1932

Abstract

Interleukin-22 (IL-22) is a recently described IL-10 family cytokine that is produced by T helper (Th) 17 cells, γδ T cells, NKT cells, and newly described innate lymphoid cells (ILCs). Knowledge of IL-22 biology has evolved rapidly since its discovery in 2000, and a role for IL-22 has been identified in numerous tissues, including the intestines, lung, liver, kidney, thymus, pancreas, and skin. IL-22 primarily targets nonhematopoietic epithelial and stromal cells, where it can promote proliferation and play a role in tissue regeneration. In addition, IL-22 regulates host defense at barrier surfaces. However, IL-22 has also been linked to several conditions involving inflammatory tissue pathology. In this review, we assess the current understanding of this cytokine, including its physiologic and pathologic effects on epithelial cell function.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-032414-112123
2015-03-21
2024-05-27
Loading full text...

Full text loading...

/deliver/fulltext/immunol/33/1/annurev-immunol-032414-112123.html?itemId=/content/journals/10.1146/annurev-immunol-032414-112123&mimeType=html&fmt=ahah

Literature Cited

  1. Dumoutier L, Van Roost E, Ameye G, Michaux L, Renauld JC. 1.  2000. IL-TIF/IL-22: genomic organization and mapping of the human and mouse genes. Genes Immun. 1:488–94 [Google Scholar]
  2. Dumoutier L, Van Roost E, Colau D, Renauld JC. 2.  2000. Human interleukin-10-related T cell-derived inducible factor: molecular cloning and functional characterization as an hepatocyte-stimulating factor. PNAS 97:10144–49 [Google Scholar]
  3. Xie MH. 3.  2000. Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R. J. Biol. Chem. 275:31335–39 [Google Scholar]
  4. Nagem RA. 4.  2002. Crystal structure of recombinant human interleukin-22. Structure 10:1051–62 [Google Scholar]
  5. de Oliveira Neto M. 5.  2008. Interleukin-22 forms dimers that are recognized by two interleukin-22R1 receptor chains. Biophys. J. 94:1754–65 [Google Scholar]
  6. Dumoutier L, Louahed J, Renauld JC. 6.  2000. Cloning and characterization of IL-10-related T cell-derived inducible factor (IL-TIF), a novel cytokine structurally related to IL-10 and inducible by IL-9. J. Immunol. 164:1814–19 [Google Scholar]
  7. Sabat R, Ouyang W, Wolk K. 7.  2014. Therapeutic opportunities of the IL-22-IL-22R1 system. Nat. Rev. Drug. Discov. 13:21–38 [Google Scholar]
  8. Xu T, Logsdon NJ, Walter MR. 8.  2005. Structure of insect-cell-derived IL-22. Acta Crystallogr. D Biol. Crystallogr. 61:942–50 [Google Scholar]
  9. Xu T, Logsdon NJ, Walter MR. 9.  2004. Crystallization and X-ray diffraction analysis of insect-cell-derived IL-22. Acta Crystallogr. D Biol. Crystallogr. 60:1295–98 [Google Scholar]
  10. Nagem RA, Ferreira Junior JR, Dumoutier L, Renauld JC, Polikarpov I. 10.  2006. Interleukin-22 and its crystal structure. Vitam. Horm. 74:77–103 [Google Scholar]
  11. Li J, Tomkinson KN, Tan XY, Wu P, Yan G. 11.  et al. 2004. Temporal associations between interleukin 22 and the extracellular domains of IL-22R and IL-10R2. Int. Immunopharmacol. 4:693–708 [Google Scholar]
  12. Kotenko SV, Krause CD, Izotova LS, Pollack BP, Wu W, Pestka S. 12.  1997. Identification and functional characterization of a second chain of the interleukin-10 receptor complex. EMBO J. 16:5894–903 [Google Scholar]
  13. Kotenko SV. 13.  2001. Identification of the functional interleukin-22 (IL-22) receptor complex: the IL-10R2 chain (IL-10Rβ) is a common chain of both the IL-10 and IL-22 (IL-10-related T cell-derived inducible factor, IL-TIF) receptor complexes. J. Biol. Chem. 276:2725–32 [Google Scholar]
  14. Jones BC, Logsdon NJ, Walter MR. 14.  2008. Structure of IL-22 bound to its high-affinity IL-22R1 chain. Structure 16:1333–44 [Google Scholar]
  15. Logsdon NJ. 15.  2004. The IL-10R2 binding hot spot on IL-22 is located on the N-terminal helix and is dependent on N-linked glycosylation. J. Mol. Biol. 342:503–14 [Google Scholar]
  16. Yoon SI. 16.  2010. Structure and mechanism of receptor sharing by the IL-10R2 common chain. Structure 18:638–48 [Google Scholar]
  17. Wolk K. 17.  2005. Is there an interaction between interleukin-10 and interleukin-22?. Genes Immun. 6:8–18 [Google Scholar]
  18. Logsdon NJ, Jones BC, Josephson K, Cook J, Walter MR. 18.  2002. Comparison of interleukin-22 and interleukin-10 soluble receptor complexes. J. Interferon Cytokine Res. 22:1099–112 [Google Scholar]
  19. Bleicher L. 19.  2008. Crystal structure of the IL-22/IL-22R1 complex and its implications for the IL-22 signaling mechanism. FEBS Lett. 582:2985–92 [Google Scholar]
  20. Reineke U, Schneider-Mergener J, Glaser RW, Stigler RD, Seifert M. 20.  et al. 1999. Evidence for conformationally different states of interleukin-10: binding of a neutralizing antibody enhances accessibility of a hidden epitope. J. Mol. Recognit. 12:242–48 [Google Scholar]
  21. Weathington NM, Snavely CA, Chen BB, Zhao J, Zhao Y, Mallampalli RK. 21.  2014. Glycogen synthase kinase-3β stabilizes the interleukin (IL)-22 receptor from proteasomal degradation in murine lung epithelia. J. Biol. Chem. 289:17610–19 [Google Scholar]
  22. Lejeune D, Dumoutier L, Constantinescu S, Kruijer W, Schuringa JJ, Renauld JC. 22.  2002. Interleukin-22 (IL-22) activates the JAK/STAT, ERK, JNK, and p38 MAP kinase pathways in a rat hepatoma cell line. Pathways that are shared with and distinct from IL-10. J. Biol. Chem. 277:33676–82 [Google Scholar]
  23. Wolk K. 23.  2004. IL-22 increases the innate immunity of tissues. Immunity 21:241–54 [Google Scholar]
  24. Spencer SD, Di Marco F, Hooley J, Pitts-Meek S, Bauer M. 24.  et al. 1998. The orphan receptor CRF2-4 is an essential subunit of the interleukin 10 receptor. J. Exp. Med. 187:571–78 [Google Scholar]
  25. Andoh A. 25.  2005. Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts. Gastroenterology 129:969–84 [Google Scholar]
  26. Ikeuchi H, Kuroiwa T, Hiramatsu N, Kaneko Y, Hiromura K. 26.  et al. 2005. Expression of interleukin-22 in rheumatoid arthritis: Potential role as a proinflammatory cytokine. Arthritis Rheum. 52:1037–46 [Google Scholar]
  27. Mitra A, Raychaudhuri SK, Raychaudhuri SP. 27.  2012. IL-22 induced cell proliferation is regulated by PI3K/Akt/mTOR signaling cascade. Cytokine 60:38–42 [Google Scholar]
  28. Wolk K. 28.  2006. IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur. J. Immunol. 36:1309–23 [Google Scholar]
  29. Wolk K, Kunz S, Asadullah K, Sabat R. 29.  2002. Cutting edge: immune cells as sources and targets of the IL-10 family members?. J. Immunol. 168:5397–402 [Google Scholar]
  30. Duhen T, Geiger R, Jarrossay D, Lanzavecchia A, Sallusto F. 30.  2009. Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nat. Immunol. 10:857–63 [Google Scholar]
  31. Chung Y. 31.  2006. Expression and regulation of IL-22 in the IL-17-producing CD4+ T lymphocytes. Cell Res. 16:902–7 [Google Scholar]
  32. Wilson NJ, Boniface K, Chan JR, McKenzie BS, Blumenschein WM. 32.  et al. 2007. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat. Immunol. 8:950–57 [Google Scholar]
  33. Basu R, O'Quinn DB, Silberger DJ, Schoeb TR, Fouser L. 33.  et al. 2012. Th22 cells are an important source of IL-22 for host protection against enteropathogenic bacteria. Immunity 37:1061–75 [Google Scholar]
  34. Liang SC, Tan X-Y, Luxenberg DP, Karim R, Dunussi-Joannopoulos K. 34.  et al. 2006. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J. Exp. Med. 203:2271–79 [Google Scholar]
  35. Mangan PR, Harrington LE, O'Quinn DB, Helms WS, Bullard DC. 35.  et al. 2006. Transforming growth factor-β induces development of the TH17 lineage. Nature 441:231–34 [Google Scholar]
  36. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB. 36.  et al. 2006. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441:235–38 [Google Scholar]
  37. Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B. 37.  2006. TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24:179–89 [Google Scholar]
  38. Zhou L, Ivanov II, Spolski R, Min R, Shenderov K. 38.  et al. 2007. IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat. Immunol. 8:967–74 [Google Scholar]
  39. Morishima N, Mizoguchi I, Takeda K, Mizuguchi J, Yoshimoto T. 39.  2009. TGF-β is necessary for induction of IL-23R and Th17 differentiation by IL-6 and IL-23. Biochem. Biophys. Res. Commun. 386:105–10 [Google Scholar]
  40. Nurieva R, Yang XO, Martinez G, Zhang Y, Panopoulos AD. 40.  et al. 2007. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448:480–83 [Google Scholar]
  41. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A. 41.  et al. 2006. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126:1121–33 [Google Scholar]
  42. Aujla SJ, Chan YR, Zheng M, Fei M, Askew DJ. 42.  et al. 2008. IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat. Med. 14:275–81 [Google Scholar]
  43. Munoz M. 43.  2009. Interleukin (IL)-23 mediates Toxoplasma gondii-induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17. J. Exp. Med. 206:3047–59 [Google Scholar]
  44. Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J. 44.  et al. 2007. Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 445:648–51 [Google Scholar]
  45. Zheng Y, Valdez PA, Danilenko DM, Hu Y, Sa SM. 45.  et al. 2008. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat. Med. 14:282–89 [Google Scholar]
  46. Zhou L, Lopes JE, Chong MM, Ivanov II, Min R. 46.  et al. 2008. TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function. Nature 453:236–40 [Google Scholar]
  47. Penel-Sotirakis K, Simonazzi E, Peguet-Navarro J, Rozieres A. 47.  2012. Differential capacity of human skin dendritic cells to polarize CD4+ T cells into IL-17, IL-21 and IL-22 producing cells. PLOS ONE 7:e45680 [Google Scholar]
  48. Rutz S, Noubade R, Eidenschenk C, Ota N, Zeng W. 48.  et al. 2011. Transcription factor c-Maf mediates the TGF-β-dependent suppression of IL-22 production in TH17 cells. Nat. Immunol. 12:1238–45 [Google Scholar]
  49. Hamada H, de la Luz Garcia-Hernandez M, Reome JB, Misra SK, Strutt TM. 49.  et al. 2009. Tc17, a unique subset of CD8 T cells that can protect against lethal influenza challenge. J. Immunol. 182:3469–81 [Google Scholar]
  50. Kondo T, Takata H, Matsuki F, Takiguchi M. 50.  2009. Cutting edge: phenotypic characterization and differentiation of human CD8+ T cells producing IL-17. J. Immunol. 182:1794–98 [Google Scholar]
  51. Ciric B, El-behi M, Cabrera R, Zhang GX, Rostami A. 51.  2009. IL-23 drives pathogenic IL-17-producing CD8+ T cells. J. Immunol. 182:5296–305 [Google Scholar]
  52. Liu Y, Yang B, Ma J, Wang H, Huang F. 52.  et al. 2011. Interleukin-21 induces the differentiation of human Tc22 cells via phosphorylation of signal transducers and activators of transcription. Immunology 132:540–48 [Google Scholar]
  53. Nograles KE. 53.  2009. IL-22-producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J. Allergy Clin. Immunol. 123:1244–52 [Google Scholar]
  54. Martin B, Hirota K, Cua DJ, Stockinger B, Veldhoen M. 54.  2009. Interleukin-17-producing γδ T cells selectively expand in response to pathogen products and environmental signals. Immunity 31:321–30 [Google Scholar]
  55. Sutton CE, Lalor SJ, Sweeney CM, Brereton CF, Lavelle EC, Mills KH. 55.  2009. Interleukin-1 and IL-23 induce innate IL-17 production from γδ T cells, amplifying Th17 responses and autoimmunity. Immunity 31:331–41 [Google Scholar]
  56. Mabuchi T, Takekoshi T, Hwang ST. 56.  2011. Epidermal CCR6+ γδ T cells are major producers of IL-22 and IL-17 in a murine model of psoriasiform dermatitis. J. Immunol. 187:5026–31 [Google Scholar]
  57. Mielke LA, Jones SA, Raverdeau M, Higgs R, Stefanska A. 57.  et al. 2013. Retinoic acid expression associates with enhanced IL-22 production by γδ T cells and innate lymphoid cells and attenuation of intestinal inflammation. J. Exp. Med. 210:1117–24 [Google Scholar]
  58. Crellin NK, Trifari S, Kaplan CD, Satoh-Takayama N, Di Santo JP, Spits H. 58.  2010. Regulation of cytokine secretion in human CD127+ LTi-like innate lymphoid cells by Toll-like receptor 2. Immunity 33:752–64 [Google Scholar]
  59. Ciofani M, Zuniga-Pflucker JC. 59.  2010. Determining γδ versus αβ T cell development. Nat. Rev. Immunol. 10:657–63 [Google Scholar]
  60. Jensen KD, Su X, Shin S, Li L, Youssef S. 60.  et al. 2008. Thymic selection determines γδ T cell effector fate: antigen-naive cells make interleukin-17 and antigen-experienced cells make interferon γ. Immunity 29:90–100 [Google Scholar]
  61. Ribot JC, deBarros A, Pang DJ, Neves JF, Peperzak V. 61.  et al. 2009. CD27 is a thymic determinant of the balance between interferon-γ- and interleukin 17-producing γδ T cell subsets. Nat. Immunol. 10:427–36 [Google Scholar]
  62. Haas JD, Gonzalez FH, Schmitz S, Chennupati V, Fohse L. 62.  et al. 2009. CCR6 and NK1.1 distinguish between IL-17A and IFN-γ-producing γδ effector T cells. Eur. J. Immunol. 39:3488–97 [Google Scholar]
  63. Shibata K, Yamada H, Nakamura R, Sun X, Itsumi M, Yoshikai Y. 63.  2008. Identification of CD25+ γδ T cells as fetal thymus-derived naturally occurring IL-17 producers. J. Immunol. 181:5940–47 [Google Scholar]
  64. Spits H, Cupedo T. 64.  2012. Innate lymphoid cells: emerging insights in development, lineage relationships, and function. Annu. Rev. Immunol. 30:647–75 [Google Scholar]
  65. Spits H, Artis D, Colonna M, Diefenbach A, Di Santo JP. 65.  et al. 2013. Innate lymphoid cells—a proposal for uniform nomenclature. Nat. Rev. Immunol. 13:145–49 [Google Scholar]
  66. Cella M, Fuchs A, Vermi W, Facchetti F, Otero K. 66.  et al. 2009. A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature 457:722–25 [Google Scholar]
  67. Luci C, Reynders A, Ivanov II, Cognet C, Chiche L. 67.  et al. 2009. Influence of the transcription factor RORγt on the development of NKp46+ cell populations in gut and skin. Nat. Immunol. 10:75–82 [Google Scholar]
  68. Sanos SL, Bui VL, Mortha A, Oberle K, Heners C. 68.  et al. 2009. RORγt and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells. Nat. Immunol. 10:83–91 [Google Scholar]
  69. Satoh-Takayama N. 69.  2008. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity 29:958–70 [Google Scholar]
  70. Cella M, Otero K, Colonna M. 70.  2010. Expansion of human NK-22 cells with IL-7, IL-2, and IL-1β reveals intrinsic functional plasticity. PNAS 107:10961–66 [Google Scholar]
  71. Colonna M. 71.  2009. Interleukin-22-producing natural killer cells and lymphoid tissue inducer-like cells in mucosal immunity. Immunity 31:15–23 [Google Scholar]
  72. Vonarbourg C, Mortha A, Bui VL, Hernandez PP, Kiss EA. 72.  et al. 2010. Regulated expression of nuclear receptor RORγt confers distinct functional fates to NK cell receptor-expressing RORγt+ innate lymphocytes. Immunity 33:736–51 [Google Scholar]
  73. Satoh-Takayama N, Lesjean-Pottier S, Vieira P, Sawa S, Eberl G. 73.  et al. 2010. IL-7 and IL-15 independently program the differentiation of intestinal CD3NKp46+ cell subsets from Id2-dependent precursors. J. Exp. Med. 207:273–80 [Google Scholar]
  74. Crellin NK, Trifari S, Kaplan CD, Cupedo T, Spits H. 74.  2010. Human NKp44+IL-22+ cells and LTi-like cells constitute a stable RORC+ lineage distinct from conventional natural killer cells. J. Exp. Med. 207:281–90 [Google Scholar]
  75. Rankin L, Groom J, Mielke LA, Seillet C, Belz GT. 75.  2013. Diversity, function, and transcriptional regulation of gut innate lymphocytes. Front. Immunol. 4:22 [Google Scholar]
  76. Sawa S, Cherrier M, Lochner M, Satoh-Takayama N, Fehling HJ. 76.  et al. 2010. Lineage relationship analysis of RORγt+ innate lymphoid cells. Science 330:665–69 [Google Scholar]
  77. Kelly KA, Scollay R. 77.  1992. Seeding of neonatal lymph nodes by T cells and identification of a novel population of CD3CD4+ cells. Eur. J. Immunol. 22:329–34 [Google Scholar]
  78. Mebius RE, Rennert P, Weissman IL. 78.  1997. Developing lymph nodes collect CD4+CD3 LTβ+ cells that can differentiate to APC, NK cells, and follicular cells but not T or B cells. Immunity 7:493–504 [Google Scholar]
  79. Sun Z, Unutmaz D, Zou YR, Sunshine MJ, Pierani A. 79.  et al. 2000. Requirement for RORγ in thymocyte survival and lymphoid organ development. Science 288:2369–73 [Google Scholar]
  80. Eberl G, Littman DR. 80.  2003. The role of the nuclear hormone receptor RORγ(t) in the development of lymph nodes and Peyer's patches. Immunol. Rev. 195:81–90 [Google Scholar]
  81. Eberl G, Marmon S, Sunshine MJ, Rennert PD, Choi Y, Littman DR. 81.  2004. An essential function for the nuclear receptor RORγt in the generation of fetal lymphoid tissue inducer cells. Nat. Immunol. 5:64–73 [Google Scholar]
  82. Cupedo T, Jansen W, Kraal G, Mebius RE. 82.  2004. Induction of secondary and tertiary lymphoid structures in the skin. Immunity 21:655–67 [Google Scholar]
  83. Finke D. 83.  2005. Fate and function of lymphoid tissue inducer cells. Curr. Opin. Immunol. 17:144–50 [Google Scholar]
  84. Withers DR, Kim MY, Bekiaris V, Rossi SW, Jenkinson WE. 84.  et al. 2007. The role of lymphoid tissue inducer cells in splenic white pulp development. Eur. J. Immunol. 37:3240–45 [Google Scholar]
  85. Scandella E, Bolinger B, Lattmann E, Miller S, Favre S. 85.  et al. 2008. Restoration of lymphoid organ integrity through the interaction of lymphoid tissue-inducer cells with stroma of the T cell zone. Nat. Immunol. 9:667–75 [Google Scholar]
  86. Tsuji M, Suzuki K, Kitamura H, Maruya M, Kinoshita K. 86.  et al. 2008. Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut. Immunity 29:261–71 [Google Scholar]
  87. Rossi SW, Kim MY, Leibbrandt A, Parnell SM, Jenkinson WE. 87.  et al. 2007. RANK signals from CD4+3 inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla. J. Exp. Med. 204:1267–72 [Google Scholar]
  88. Yoshida H, Honda K, Shinkura R, Adachi S, Nishikawa S. 88.  et al. 1999. IL-7 receptor α+ CD3 cells in the embryonic intestine induces the organizing center of Peyer's patches. Int. Immunol. 11:643–55 [Google Scholar]
  89. van de Pavert SA, Olivier BJ, Goverse G, Vondenhoff MF, Greuter M. 89.  et al. 2009. Chemokine CXCL13 is essential for lymph node initiation and is induced by retinoic acid and neuronal stimulation. Nat. Immunol. 10:1193–99 [Google Scholar]
  90. Takatori H, Kanno Y, Watford WT, Tato CM, Weiss G. 90.  et al. 2009. Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22. J. Exp. Med. 206:35–41 [Google Scholar]
  91. Cupedo T, Crellin NK, Papazian N, Rombouts EJ, Weijer K. 91.  et al. 2009. Human fetal lymphoid tissue-inducer cells are interleukin 17-producing precursors to RORC+ CD127+ natural killer-like cells. Nat. Immunol. 10:66–74 [Google Scholar]
  92. Hazenberg MD, Spits H. 92.  2014. Human innate lymphoid cells. Blood 124:700–9 [Google Scholar]
  93. Buonocore S, Ahern PP, Uhlig HH, Ivanov II, Littman DR. 93.  et al. 2010. Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology. Nature 464:1371–75 [Google Scholar]
  94. Sciume G, Hirahara K, Takahashi H, Laurence A, Villarino AV. 94.  et al. 2012. Distinct requirements for T-bet in gut innate lymphoid cells. J. Exp. Med. 209:2331–38 [Google Scholar]
  95. Rankin LC, Groom JR, Chopin M, Herold MJ, Walker JA. 95.  et al. 2013. The transcription factor T-bet is essential for the development of NKp46+ innate lymphocytes via the Notch pathway. Nat. Immunol. 14:389–95 [Google Scholar]
  96. Klose CS, Kiss EA, Schwierzeck V, Ebert K, Hoyler T. 96.  et al. 2013. A T-bet gradient controls the fate and function of CCR6-RORγt+ innate lymphoid cells. Nature 494:261–65 [Google Scholar]
  97. Hughes T, Briercheck EL, Freud AG, Trotta R, McClory S. 97.  et al. 2014. The transcription factor AHR prevents the differentiation of a stage 3 innate lymphoid cell subset to natural killer cells. Cell Rep. 8:150–62 [Google Scholar]
  98. Possot C, Schmutz S, Chea S, Boucontet L, Louise A. 98.  et al. 2011. Notch signaling is necessary for adult, but not fetal, development of RORγt+ innate lymphoid cells. Nat. Immunol. 12:949–58 [Google Scholar]
  99. Mebius RE, Miyamoto T, Christensen J, Domen J, Cupedo T. 99.  et al. 2001. The fetal liver counterpart of adult common lymphoid progenitors gives rise to all lymphoid lineages, CD45+CD4+CD3 cells, as well as macrophages. J. Immunol. 166:6593–601 [Google Scholar]
  100. Yokota Y, Mansouri A, Mori S, Sugawara S, Adachi S. 100.  et al. 1999. Development of peripheral lymphoid organs and natural killer cells depends on the helix-loop-helix inhibitor Id2. Nature 397:702–6 [Google Scholar]
  101. Hoyler T, Klose CS, Souabni A, Turqueti-Neves A, Pfeifer D. 101.  et al. 2012. The transcription factor GATA-3 controls cell fate and maintenance of type 2 innate lymphoid cells. Immunity 37:634–48 [Google Scholar]
  102. Klose CN, Flach M, Möhle L, Rogell L, Hoyler T. 102.  et al. 2014. Differentiation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages. Cell 157:340–56 [Google Scholar]
  103. Welner RS, Pelayo R, Kincade PW. 103.  2008. Evolving views on the genealogy of B cells. Nat. Rev. Immunol. 8:95–106 [Google Scholar]
  104. Lin H, Grosschedl R. 104.  1995. Failure of B-cell differentiation in mice lacking the transcription factor EBF. Nature 376:263–67 [Google Scholar]
  105. Nechanitzky R, Akbas D, Scherer S, Gyory I, Hoyler T. 105.  et al. 2013. Transcription factor EBF1 is essential for the maintenance of B cell identity and prevention of alternative fates in committed cells. Nat. Immunol. 14:867–75 [Google Scholar]
  106. Boos MD, Yokota Y, Eberl G, Kee BL. 106.  2007. Mature natural killer cell and lymphoid tissue-inducing cell development requires Id2-mediated suppression of E protein activity. J. Exp. Med. 204:1119–30 [Google Scholar]
  107. Bain G, Maandag EC, Izon DJ, Amsen D, Kruisbeek AM. 107.  et al. 1994. E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements. Cell 79:885–92 [Google Scholar]
  108. Cherrier M, Sawa S, Eberl G. 108.  2012. Notch, Id2, and RORγt sequentially orchestrate the fetal development of lymphoid tissue inducer cells. J. Exp. Med. 209:729–40 [Google Scholar]
  109. Constantinides MG, McDonald BD, Verhoef PA, Bendelac A. 109.  2014. A committed precursor to innate lymphoid cells. Nature 508:397–401 [Google Scholar]
  110. Geiger TL, Abt MC, Gasteiger G, Firth MA, O'Connor MH. 110.  et al. 2014. Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens. J. Exp. Med. 211:1723–31 [Google Scholar]
  111. Seillet C, Rankin LC, Groom JR, Mielke LA, Tellier J. 111.  et al. 2014. Nfil3 is required for the development of all innate lymphoid cell subsets. J. Exp. Med. 211:1733–40 [Google Scholar]
  112. Male V, Nisoli I, Kostrzewski T, Allan DSJ, Carlyle JR. 112.  et al. 2014. The transcription factor E4bp4/Nfil3 controls commitment to the NK lineage and directly regulates Eomes and Id2 expression. J. Exp. Med. 211:635–42 [Google Scholar]
  113. Rothenberg EV, Moore JE, Yui MA. 113.  2008. Launching the T-cell-lineage developmental programme. Nat. Rev. Immunol. 8:9–21 [Google Scholar]
  114. Klein Wolterink RG, Serafini N, van Nimwegen M, Vosshenrich CA, de Bruijn MJ. 114.  et al. 2013. Essential, dose-dependent role for the transcription factor Gata3 in the development of IL-5+ and IL-13+ type 2 innate lymphoid cells. PNAS 110:10240–45 [Google Scholar]
  115. Mjosberg J, Bernink J, Golebski K, Karrich JJ, Peters CP. 115.  et al. 2012. The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells. Immunity 37:649–59 [Google Scholar]
  116. Serafini N, Klein Wolterink RG, Satoh-Takayama N, Xu W, Vosshenrich CA. 116.  et al. 2014. Gata3 drives development of RORγt+ group 3 innate lymphoid cells. J. Exp. Med. 211:199–208 [Google Scholar]
  117. Goto M, Murakawa M, Kadoshima-Yamaoka K, Tanaka Y, Nagahira K. 117.  et al. 2009. Murine NKT cells produce Th17 cytokine interleukin-22. Cell Immunol. 254:81–84 [Google Scholar]
  118. Juno JA, Keynan Y, Fowke KR. 118.  2012. Invariant NKT cells: regulation and function during viral infection. PLOS Pathog. 8:e1002838 [Google Scholar]
  119. Moreira-Teixeira L, Resende M, Coffre M, Devergne O, Herbeuval JP. 119.  et al. 2011. Proinflammatory environment dictates the IL-17-producing capacity of human invariant NKT cells. J. Immunol. 186:5758–65 [Google Scholar]
  120. Paget C, Ivanov S, Fontaine J, Renneson J, Blanc F. 120.  et al. 2012. Interleukin-22 is produced by invariant natural killer T lymphocytes during influenza A virus infection: potential role in protection against lung epithelial damages. J. Biol. Chem. 287:8816–29 [Google Scholar]
  121. Godfrey DI, Stankovic S, Baxter AG. 121.  2010. Raising the NKT cell family. Nat. Immunol. 11:197–206 [Google Scholar]
  122. Coquet JM, Chakravarti S, Kyparissoudis K, McNab FW, Pitt LA. 122.  et al. 2008. Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4NK1.1 NKT cell population. PNAS 105:11287–92 [Google Scholar]
  123. Doisne JM, Becourt C, Amniai L, Duarte N, Le Luduec JB. 123.  et al. 2009. Skin and peripheral lymph node invariant NKT cells are mainly retinoic acid receptor-related orphan receptor γt+ and respond preferentially under inflammatory conditions. J. Immunol. 183:2142–49 [Google Scholar]
  124. Michel ML, Mendes-da-Cruz D, Keller AC, Lochner M, Schneider E. 124.  et al. 2008. Critical role of ROR-γt in a new thymic pathway leading to IL-17-producing invariant NKT cell differentiation. PNAS 105:19845–50 [Google Scholar]
  125. Doisne JM, Soulard V, Becourt C, Amniai L, Henrot P. 125.  et al. 2011. Cutting edge: crucial role of IL-1 and IL-23 in the innate IL-17 response of peripheral lymph node NK1.1 invariant NKT cells to bacteria. J. Immunol. 186:662–66 [Google Scholar]
  126. Rachitskaya AV, Hansen AM, Horai R, Li Z, Villasmil R. 126.  et al. 2008. Cutting edge: NKT cells constitutively express IL-23 receptor and RORγt and rapidly produce IL-17 upon receptor ligation in an IL-6-independent fashion. J. Immunol. 180:5167–71 [Google Scholar]
  127. Raifer H, Mahiny AJ, Bollig N, Petermann F, Hellhund A. 127.  et al. 2012. Unlike αβ T cells, γδ T cells, LTi cells and NKT cells do not require IRF4 for the production of IL-17A and IL-22. Eur. J. Immunol. 42:3189–201 [Google Scholar]
  128. Bendelac A, Savage PB, Teyton L. 128.  2007. The biology of NKT cells. Annu. Rev. Immunol. 25:297–336 [Google Scholar]
  129. Benlagha K, Wei DG, Veiga J, Teyton L, Bendelac A. 129.  2005. Characterization of the early stages of thymic NKT cell development. J. Exp. Med. 202:485–92 [Google Scholar]
  130. Webster KE, Kim HO, Kyparissoudis K, Corpuz TM, Pinget GV. 130.  et al. 2014. IL-17-producing NKT cells depend exclusively on IL-7 for homeostasis and survival. Mucosal Immunol. 7:1058–67 [Google Scholar]
  131. Hansson M, Silverpil E, Linden A, Glader P. 131.  2013. Interleukin-22 produced by alveolar macrophages during activation of the innate immune response. Inflamm. Res. 62:561–69 [Google Scholar]
  132. Zindl CL, Lai JF, Lee YK, Maynard CL, Harbour SN. 132.  et al. 2013. IL-22-producing neutrophils contribute to antimicrobial defense and restitution of colonic epithelial integrity during colitis. PNAS 110:12768–73 [Google Scholar]
  133. Kastelein RA, Hunter CA, Cua DJ. 133.  2007. Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annu. Rev. Immunol. 25:221–42 [Google Scholar]
  134. Hunter CA. 134.  2005. New IL-12-family members: IL-23 and IL-27, cytokines with divergent functions. Nat. Rev. Immunol. 5:521–31 [Google Scholar]
  135. Gerosa F, Baldani-Guerra B, Lyakh LA, Batoni G, Esin S. 135.  et al. 2008. Differential regulation of interleukin 12 and interleukin 23 production in human dendritic cells. J. Exp. Med. 205:1447–61 [Google Scholar]
  136. Sonnenberg GF, Monticelli LA, Elloso MM, Fouser LA, Artis D. 136.  2011. CD4+ lymphoid tissue-inducer cells promote innate immunity in the gut. Immunity 34:122–34 [Google Scholar]
  137. Hanash AM, Dudakov JA, Hua G, O'Connor MH, Young LF. 137.  et al. 2012. Interleukin-22 protects intestinal stem cells from immune-mediated tissue damage and regulates sensitivity to graft versus host disease. Immunity 37:339–50 [Google Scholar]
  138. Dudakov JA, Hanash AM, Jenq RR, Young LF, Ghosh A. 138.  et al. 2012. Interleukin-22 drives endogenous thymic regeneration in mice. Science 336:91–95 [Google Scholar]
  139. Kinnebrew MA, Buffie CG, Diehl GE, Zenewicz LA, Leiner I. 139.  et al. 2012. Interleukin 23 production by intestinal CD103+CD11b+ dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense. Immunity 36:276–87 [Google Scholar]
  140. Satpathy AT, Briseno CG, Lee JS, Ng D, Manieri NA. 140.  et al. 2013. Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens. Nat. Immunol. 14:937–48 [Google Scholar]
  141. Siddiqui KR, Laffont S, Powrie F. 141.  2010. E-cadherin marks a subset of inflammatory dendritic cells that promote T cell-mediated colitis. Immunity 32:557–67 [Google Scholar]
  142. Manta C, Heupel E, Radulovic K, Rossini V, Garbi N. 142.  et al. 2013. CX(3)CR1+ macrophages support IL-22 production by innate lymphoid cells during infection with Citrobacter rodentium. Mucosal Immunol. 6:177–88 [Google Scholar]
  143. Niess JH, Adler G. 143.  2010. Enteric flora expands gut lamina propria CX3CR1+ dendritic cells supporting inflammatory immune responses under normal and inflammatory conditions. J. Immunol. 184:2026–37 [Google Scholar]
  144. Longman RS, Diehl GE, Victorio DA, Huh JR, Galan C. 144.  et al. 2014. CX3CR1+ mononuclear phagocytes support colitis-associated innate lymphoid cell production of IL-22. J. Exp. Med. 211:1571–83 [Google Scholar]
  145. Roses RE, Xu S, Xu M, Koldovsky U, Koski G, Czerniecki BJ. 145.  2008. Differential production of IL-23 and IL-12 by myeloid-derived dendritic cells in response to TLR agonists. J. Immunol. 181:5120–27 [Google Scholar]
  146. Paustian C, Taylor P, Johnson T, Xu M, Ramirez N. 146.  et al. 2013. Extracellular ATP and Toll-like receptor 2 agonists trigger in human monocytes an activation program that favors T helper 17. PLOS ONE 8:e54804 [Google Scholar]
  147. Peral de Castro C, Jones SA, Ní Cheallaigh C, Hearnden CA, Williams L. 147.  et al. 2012. Autophagy regulates IL-23 secretion and innate T cell responses through effects on IL-1 secretion. J. Immunol. 189:4144–53 [Google Scholar]
  148. Flutter B, Nestle FO. 148.  2013. TLRs to cytokines: mechanistic insights from the imiquimod mouse model of psoriasis. Eur. J. Immunol. 43:3138–46 [Google Scholar]
  149. van der Fits L, Mourits S, Voerman JS, Kant M, Boon L. 149.  et al. 2009. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J. Immunol. 182:5836–45 [Google Scholar]
  150. Lyakh L, Trinchieri G, Provezza L, Carra G, Gerosa F. 150.  2008. Regulation of interleukin-12/interleukin-23 production and the T-helper 17 response in humans. Immunol. Rev. 226:112–31 [Google Scholar]
  151. Brain O, Owens BMJ, Pichulik T, Allan P, Khatamzas E. 151.  et al. 2013. The intracellular sensor NOD2 induces microRNA-29 expression in human dendritic cells to limit IL-23 release. Immunity 39:521–36 [Google Scholar]
  152. Xue X, Feng T, Yao S, Wolf KJ, Liu CG. 152.  et al. 2011. Microbiota downregulates dendritic cell expression of miR-10a, which targets IL-12/IL-23p40. J. Immunol. 187:5879–86 [Google Scholar]
  153. Sender LY, Gibbert K, Suezer Y, Radeke HH, Kalinke U, Waibler Z. 153.  2010. CD40 ligand-triggered human dendritic cells mount interleukin-23 responses that are further enhanced by danger signals. Mol. Immunol. 47:1255–61 [Google Scholar]
  154. Zheng M, Rapaka RR, Yu AC, Shellito JE, Kolls JK. 154.  2011. Role of interleukin-23-dependent antifungal immune responses in dendritic cell-vaccinated mice. Infect. Immun. 79:3778–83 [Google Scholar]
  155. Ma X, Chow JM, Gri G, Carra G, Gerosa F. 155.  et al. 1996. The interleukin 12 p40 gene promoter is primed by interferon γ in monocytic cells. J. Exp. Med. 183:147–57 [Google Scholar]
  156. Qian X, Ning H, Zhang J, Hoft DF, Stumpo DJ. 156.  et al. 2011. Posttranscriptional regulation of IL-23 expression by IFN-γ through tristetraprolin. J. Immunol. 186:6454–64 [Google Scholar]
  157. Zakharova M, Ziegler HK. 157.  2005. Paradoxical anti-inflammatory actions of TNF-α: inhibition of IL-12 and IL-23 via TNF receptor 1 in macrophages and dendritic cells. J. Immunol. 175:5024–33 [Google Scholar]
  158. Riol-Blanco L, Ordovas-Montanes J, Perro M, Naval E, Thiriot A. 158.  et al. 2014. Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation. Nature 510:157–61 [Google Scholar]
  159. Vassiliou E, Sharma V, Jing H, Sheibanie F, Ganea D. 159.  2004. Prostaglandin E2 promotes the survival of bone marrow-derived dendritic cells. J. Immunol. 173:6955–64 [Google Scholar]
  160. Schirmer C, Klein C, von Bergen M, Simon JC, Saalbach A. 160.  2010. Human fibroblasts support the expansion of IL-17-producing T cells via up-regulation of IL-23 production by dendritic cells. Blood 116:1715–25 [Google Scholar]
  161. Sheibanie AF, Tadmori I, Jing H, Vassiliou E, Ganea D. 161.  2004. Prostaglandin E2 induces IL-23 production in bone marrow-derived dendritic cells. FASEB J. 18:1318–20 [Google Scholar]
  162. Schnurr M, Toy T, Shin A, Wagner M, Cebon J, Maraskovsky E. 162.  2005. Extracellular nucleotide signaling by P2 receptors inhibits IL-12 and enhances IL-23 expression in human dendritic cells: a novel role for the cAMP pathway. Blood 105:1582–89 [Google Scholar]
  163. Satoh-Takayama N, Lesjean-Pottier S, Sawa S, Vosshenrich CAJ, Eberl G, Di Santo JP. 163.  2011. Lymphotoxin-β receptor-independent development of intestinal IL-22-producing NKp46+ innate lymphoid cells. Eur. J. Immunol. 41:780–86 [Google Scholar]
  164. Ota N, Wong K, Valdez PA, Zheng Y, Crellin NK. 164.  et al. 2011. IL-22 bridges the lymphotoxin pathway with the maintenance of colonic lymphoid structures during infection with Citrobacter rodentium. Nat. Immunol. 12:941–48 [Google Scholar]
  165. Tumanov AV, Koroleva EP, Guo X, Wang Y, Kruglov A. 165.  et al. 2011. Lymphotoxin controls the IL-22 protection pathway in gut innate lymphoid cells during mucosal pathogen challenge. Cell Host Microbe 10:44–53 [Google Scholar]
  166. Upadhyay V, Poroyko V, Kim TJ, Devkota S, Fu S. 166.  et al. 2012. Lymphotoxin regulates commensal responses to enable diet-induced obesity. Nat. Immunol. 13:947–53 [Google Scholar]
  167. Ware CF. 167.  2005. Network communications: lymphotoxins, LIGHT, and TNF. Annu. Rev. Immunol. 23:787–819 [Google Scholar]
  168. Tumanov AV, Grivennikov SI, Shakhov AN, Rybtsov SA, Koroleva EP. 168.  et al. 2003. Dissecting the role of lymphotoxin in lymphoid organs by conditional targeting. Immunol. Rev. 195:106–16 [Google Scholar]
  169. Monteiro M, Almeida CF, Agua-Doce A, Graca L. 169.  2013. Induced IL-17-producing invariant NKT cells require activation in presence of TGF-β and IL-1β. J. Immunol. 190:805–11 [Google Scholar]
  170. Lee Y, Kumagai Y, Jang MS, Kim JH, Yang BG. 170.  et al. 2013. Intestinal Linc-Kit+NKp46 CD4 population strongly produces IL-22 upon IL-1β stimulation. J. Immunol. 190:5296–305 [Google Scholar]
  171. Chen VL, Surana NK, Duan J, Kasper DL. 171.  2013. Role of murine intestinal interleukin-1 receptor 1-expressing lymphoid tissue inducer-like cells in Salmonella infection. PLOS ONE 8:e65405 [Google Scholar]
  172. Sims JE, Smith DE. 172.  2010. The IL-1 family: regulators of immunity. Nat. Rev. Immunol. 10:89–102 [Google Scholar]
  173. Shaw MH, Kamada N, Kim YG, Núñez G. 173.  2012. Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state TH17 cells in the intestine. J. Exp. Med. 209:251–58 [Google Scholar]
  174. Hughes T, Becknell B, Freud AG, McClory S, Briercheck E. 174.  et al. 2010. Interleukin-1β selectively expands and sustains interleukin-22+ immature human natural killer cells in secondary lymphoid tissue. Immunity 32:803–14 [Google Scholar]
  175. Vonarbourg C, Diefenbach A. 175.  2012. Multifaceted roles of interleukin-7 signaling for the development and function of innate lymphoid cells. Semin. Immunol. 24:165–74 [Google Scholar]
  176. von Freeden-Jeffry U, Vieira P, Lucian LA, McNeil T, Burdach SE, Murray R. 176.  1995. Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J. Exp. Med. 181:1519–26 [Google Scholar]
  177. Peschon JJ, Morrissey PJ, Grabstein KH, Ramsdell FJ, Maraskovsky E. 177.  et al. 1994. Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J. Exp. Med. 180:1955–60 [Google Scholar]
  178. Adachi S, Yoshida H, Honda K, Maki K, Saijo K. 178.  et al. 1998. Essential role of IL-7 receptor α in the formation of Peyer's patch anlage. Int. Immunol. 10:1–6 [Google Scholar]
  179. Luther SA, Ansel KM, Cyster JG. 179.  2003. Overlapping roles of CXCL13, interleukin 7 receptor α, and CCR7 ligands in lymph node development. J. Exp. Med. 197:1191–98 [Google Scholar]
  180. Chappaz S, Finke D. 180.  2010. The IL-7 signaling pathway regulates lymph node development independent of peripheral lymphocytes. J. Immunol. 184:3562–69 [Google Scholar]
  181. Cao X, Shores EW, Hu-Li J, Anver MR, Kelsall BL. 181.  et al. 1995. Defective lymphoid development in mice lacking expression of the common cytokine receptor γ chain. Immunity 2:223–38 [Google Scholar]
  182. Park SY, Saijo K, Takahashi T, Osawa M, Arase H. 182.  et al. 1995. Developmental defects of lymphoid cells in Jak3 kinase-deficient mice. Immunity 3:771–82 [Google Scholar]
  183. Meier D, Bornmann C, Chappaz S, Schmutz S, Otten LA. 183.  et al. 2007. Ectopic lymphoid-organ development occurs through interleukin 7-mediated enhanced survival of lymphoid-tissue-inducer cells. Immunity 26:643–54 [Google Scholar]
  184. De Togni P, Goellner J, Ruddle NH, Streeter PR, Fick A. 184.  et al. 1994. Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science 264:703–7 [Google Scholar]
  185. Honda K, Nakano H, Yoshida H, Nishikawa S, Rennert P. 185.  et al. 2001. Molecular basis for hematopoietic/mesenchymal interaction during initiation of Peyer's patch organogenesis. J. Exp. Med. 193:621–30 [Google Scholar]
  186. Yoshida H, Naito A, Inoue J, Satoh M, Santee-Cooper SM. 186.  et al. 2002. Different cytokines induce surface lymphotoxin-αβ on IL-7 receptor-α cells that differentially engender lymph nodes and Peyer's patches. Immunity 17:823–33 [Google Scholar]
  187. Qiu J, Heller JJ, Guo X, Chen Z-mE, Fish K. 187.  et al. 2012. The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. Immunity 36:92–104 [Google Scholar]
  188. Korn LL, Thomas HL, Hubbeling HG, Spencer SP, Sinha R. 188.  et al. 2014. Conventional CD4+ T cells regulate IL-22-producing intestinal innate lymphoid cells. Mucosal Immunol. 7:1045–57 [Google Scholar]
  189. Spencer SP, Wilhelm C, Yang Q, Hall JA, Bouladoux N. 189.  et al. 2014. Adaptation of innate lymphoid cells to a micronutrient deficiency promotes type 2 barrier immunity. Science 343:432–37 [Google Scholar]
  190. Lee JS, Cella M, McDonald KG, Garlanda C, Kennedy GD. 190.  et al. 2012. AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch. Nat. Immunol. 13:144–51 [Google Scholar]
  191. Veldhoen M, Hirota K, Westendorf AM, Buer J, Dumoutier L. 191.  et al. 2008. The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 453:106–9 [Google Scholar]
  192. Esser C, Rannug A, Stockinger B. 192.  2009. The aryl hydrocarbon receptor in immunity. Trends Immunol. 30:447–54 [Google Scholar]
  193. Nguyen LP, Bradfield CA. 193.  2008. The search for endogenous activators of the aryl hydrocarbon receptor. Chem. Res. Toxicol. 21:102–16 [Google Scholar]
  194. Denison MS, Nagy SR. 194.  2003. Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals. Annu. Rev. Pharmacol. Toxicol. 43:309–34 [Google Scholar]
  195. McMillan BJ, Bradfield CA. 195.  2007. The aryl hydrocarbon receptor is activated by modified low-density lipoprotein. PNAS 104:1412–17 [Google Scholar]
  196. Oesch-Bartlomowicz B, Huelster A, Wiss O, Antoniou-Lipfert P, Dietrich C. 196.  et al. 2005. Aryl hydrocarbon receptor activation by cAMP versus dioxin: divergent signaling pathways. PNAS 102:9218–23 [Google Scholar]
  197. Puga A, Ma C, Marlowe JL. 197.  2009. The aryl hydrocarbon receptor cross-talks with multiple signal transduction pathways. Biochem. Pharmacol. 77:713–22 [Google Scholar]
  198. Lowe MM, Mold JE, Kanwar B, Huang Y, Louie A. 198.  et al. 2014. Identification of cinnabarinic acid as a novel endogenous aryl hydrocarbon receptor ligand that drives IL-22 production. PLOS ONE 9:e87877 [Google Scholar]
  199. Qiu J, Guo X, Chen Z-ming E, He L, Sonnenberg GF. 199.  et al. 2013. Group 3 innate lymphoid cells inhibit T-cell-mediated intestinal inflammation through aryl hydrocarbon receptor signaling and regulation of microflora. Immunity 39:386–99 [Google Scholar]
  200. Zelante T, Iannitti RG, Cunha C, De Luca A, Giovannini G. 200.  et al. 2013. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity 39:372–85 [Google Scholar]
  201. Maillard I, Fang T, Pear WS. 201.  2005. Regulation of lymphoid development, differentiation, and function by the Notch pathway. Annu. Rev. Immunol. 23:945–74 [Google Scholar]
  202. Mielke LA, Groom JR, Rankin LC, Seillet C, Masson F. 202.  et al. 2013. TCF-1 controls ILC2 and NKp46+RORγt+ innate lymphocyte differentiation and protection in intestinal inflammation. J. Immunol. 191:4383–91 [Google Scholar]
  203. Alam MS, Maekawa Y, Kitamura A, Tanigaki K, Yoshimoto T. 203.  et al. 2010. Notch signaling drives IL-22 secretion in CD4+ T cells by stimulating the aryl hydrocarbon receptor. PNAS 107:5943–48 [Google Scholar]
  204. Xu M, Morishima N, Mizoguchi I, Chiba Y, Fujita K. 204.  et al. 2011. Regulation of the development of acute hepatitis by IL-23 through IL-22 and IL-17 production. Eur. J. Immunol. 41:2828–39 [Google Scholar]
  205. Bhuyan ZA, Asanoma M, Iwata A, Ishifune C, Maekawa Y. 205.  et al. 2014. Abrogation of Rbpj attenuates experimental autoimmune uveoretinitis by inhibiting IL-22-producing CD4+ T cells. PLOS ONE 9:e89266 [Google Scholar]
  206. Mukherjee S, Schaller MA, Neupane R, Kunkel SL, Lukacs NW. 206.  2009. Regulation of T cell activation by Notch ligand, DLL4, promotes IL-17 production and Rorc activation. J. Immunol. 182:7381–88 [Google Scholar]
  207. Kamakura S, Oishi K, Yoshimatsu T, Nakafuku M, Masuyama N, Gotoh Y. 207.  2004. Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling. Nat. Cell Biol. 6:547–54 [Google Scholar]
  208. Murano T, Okamoto R, Ito G, Nakata T, Hibiya S. 208.  et al. 2014. Hes1 promotes the IL-22-mediated antimicrobial response by enhancing STAT3-dependent transcription in human intestinal epithelial cells. Biochem. Biophys. Res. Commun. 443:840–46 [Google Scholar]
  209. Weiss B. 209.  2004. Cloning of murine IL-22 receptor alpha 2 and comparison with its human counterpart. Genes Immun. 5:330–36 [Google Scholar]
  210. Gruenberg BH. 210.  2001. A novel, soluble homologue of the human IL-10 receptor with preferential expression in placenta. Genes Immun. 2:329–34 [Google Scholar]
  211. Kotenko SV, Izotova LS, Mirochnitchenko OV, Esterova E, Dickensheets H. 211.  et al. 2001. Identification, cloning, and characterization of a novel soluble receptor that binds IL-22 and neutralizes its activity. J. Immunol. 166:7096–103 [Google Scholar]
  212. Dumoutier L, Lejeune D, Colau D, Renauld JC. 212.  2001. Cloning and characterization of IL-22 binding protein, a natural antagonist of IL-10-related T cell-derived inducible factor/IL-22. J. Immunol. 166:7090–95 [Google Scholar]
  213. Wei CC, Ho TW, Liang WG, Chen GY, Chang MS. 213.  2003. Cloning and characterization of mouse IL-22 binding protein. Genes Immun. 4:204–11 [Google Scholar]
  214. Xu W, Presnell SR, Parrish-Novak J, Kindsvogel W, Jaspers S. 214.  et al. 2001. A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist. PNAS 98:9511–16 [Google Scholar]
  215. Wu PW. 215.  2008. IL-22R, IL-10R2, and IL-22BP binding sites are topologically juxtaposed on adjacent and overlapping surfaces of IL-22. J. Mol. Biol. 382:1168–83 [Google Scholar]
  216. de Moura PR. 216.  2009. Crystal structure of a soluble decoy receptor IL-22BP bound to interleukin-22. FEBS Lett. 583:1072–77 [Google Scholar]
  217. Wolk K. 217.  2007. IL-22 induces lipopolysaccharide-binding protein in hepatocytes: a potential systemic role of IL-22 in Crohn's disease. J. Immunol. 178:5973–81 [Google Scholar]
  218. Martin JC, Beriou G, Heslan M, Chauvin C, Utriainen L. 218.  et al. 2014. Interleukin-22 binding protein (IL-22BP) is constitutively expressed by a subset of conventional dendritic cells and is strongly induced by retinoic acid. Mucosal Immunol. 7:101–13 [Google Scholar]
  219. Lecart S, Morel F, Noraz N, Pene J, Garcia M. 219.  et al. 2002. IL-22, in contrast to IL-10, does not induce Ig production, due to absence of a functional IL-22 receptor on activated human B cells. Int. Immunol. 14:1351–56 [Google Scholar]
  220. Huber S, Gagliani N, Zenewicz LA, Huber FJ, Bosurgi L. 220.  et al. 2012. IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine. Nature 491:259–63 [Google Scholar]
  221. Sugimoto K, Ogawa A, Mizoguchi E, Shimomura Y, Andoh A. 221.  et al. 2008. IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. J. Clin. Investig. 118:534–44 [Google Scholar]
  222. Volpe E, Touzot M, Servant N, Marloie-Provost MA, Hupe P. 222.  et al. 2009. Multiparametric analysis of cytokine-driven human Th17 differentiation reveals a differential regulation of IL-17 and IL-22 production. Blood 114:3610–14 [Google Scholar]
  223. Valdez PA, Vithayathil PJ, Janelsins BM, Shaffer AL, Williamson PR, Datta SK. 223.  2012. Prostaglandin E2 suppresses antifungal immunity by inhibiting interferon regulatory factor 4 function and interleukin-17 expression in T cells. Immunity 36:668–79 [Google Scholar]
  224. Brustle A, Heink S, Huber M, Rosenplanter C, Stadelmann C. 224.  et al. 2007. The development of inflammatory TH-17 cells requires interferon-regulatory factor 4. Nat. Immunol. 8:958–66 [Google Scholar]
  225. Wang H, Li Z, Yang B, Yu S, Wu C. 225.  2013. IL-27 suppresses the production of IL-22 in human CD4+ T cells by inducing the expression of SOCS1. Immunol. Lett. 152:96–103 [Google Scholar]
  226. Liu H, Rohowsky-Kochan C. 226.  2011. Interleukin-27-mediated suppression of human Th17 cells is associated with activation of STAT1 and suppressor of cytokine signaling protein 1. J. Interferon Cytokine Res. 31:459–69 [Google Scholar]
  227. Paulos CM, Carpenito C, Plesa G, Suhoski MM, Varela-Rohena A. 227.  et al. 2010. The inducible costimulator (ICOS) is critical for the development of human TH17 cells. Sci. Transl. Med. 2:55ra78 [Google Scholar]
  228. Bauquet AT, Jin H, Paterson AM, Mitsdoerffer M, Ho IC. 228.  et al. 2009. The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells. Nat. Immunol. 10:167–75 [Google Scholar]
  229. van de Veerdonk FL, Stoeckman AK, Wu G, Boeckermann AN, Azam T. 229.  et al. 2012. IL-38 binds to the IL-36 receptor and has biological effects on immune cells similar to IL-36 receptor antagonist. PNAS 109:3001–5 [Google Scholar]
  230. Tortola L, Rosenwald E, Abel B, Blumberg H, Schafer M. 230.  et al. 2012. Psoriasiform dermatitis is driven by IL-36-mediated DC-keratinocyte crosstalk. J. Clin. Investig. 122:3965–76 [Google Scholar]
  231. Witte E, Witte K, Warszawska K, Sabat R, Wolk K. 231.  2010. Interleukin-22: a cytokine produced by T, NK and NKT cell subsets, with importance in the innate immune defense and tissue protection. Cytokine Growth Factor Rev. 21:365–79 [Google Scholar]
  232. Sonnenberg GF, Fouser LA, Artis D. 232.  2011. Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nat. Immunol. 12:383–90 [Google Scholar]
  233. Cordero-Coma M, Calleja S, Llorente M, Rodriguez E, Franco M, Ruiz de Morales JG. 233.  2013. Serum cytokine profile in adalimumab-treated refractory uveitis patients: decreased IL-22 correlates with clinical responses. Ocul. Immunol. Inflamm. 21:212–19 [Google Scholar]
  234. Dalmas E, Venteclef N, Caer C, Poitou C, Cremer I. 234.  et al. 2014. T cell-derived IL-22 amplifies IL-1β-driven inflammation in human adipose tissue: relevance to obesity and type 2 diabetes. Diabetes 63:1966–77 [Google Scholar]
  235. Fabbrini E, Cella M, McCartney SA, Fuchs A, Abumrad NA. 235.  et al. 2013. Association between specific adipose tissue CD4+ T-cell populations and insulin resistance in obese individuals. Gastroenterology 145:366–74.e3 [Google Scholar]
  236. Kong Q, Xue Y, Wu W, Yang F, Liu Y. 236.  et al. 2013. IL-22 exacerbates the severity of CVB3-induced acute viral myocarditis in IL-17A-deficient mice. Mol. Med. Rep. 7:1329–35 [Google Scholar]
  237. Rainard P, Cunha P, Bougarn S, Fromageau A, Rossignol C. 237.  et al. 2013. T helper 17-associated cytokines are produced during antigen-specific inflammation in the mammary gland. PLOS ONE 8:e63471 [Google Scholar]
  238. Sugita S, Kawazoe Y, Imai A, Kawaguchi T, Horie S. 238.  et al. 2013. Role of IL-22- and TNF-α-producing Th22 cells in uveitis patients with Behcet's disease. J. Immunol. 190:5799–808 [Google Scholar]
  239. Sugita S, Kawazoe Y, Imai A, Usui Y, Takahashi M, Mochizuki M. 239.  2013. Suppression of IL-22-producing T helper 22 cells by RPE cells via PD-L1/PD-1 interactions. Investig. Ophthalmol. Vis. Sci. 54:6926–33 [Google Scholar]
  240. Zaidi T, Zaidi T, Cywes-Bentley C, Lu R, Priebe GP, Pier GB. 240.  2014. Microbiota-driven immune cellular maturation is essential for antibody-mediated adaptive immunity to Staphylococcus aureus infection in the eye. Infect. Immun. 82:3483–91 [Google Scholar]
  241. Mortha A, Chudnovskiy A, Hashimoto D, Bogunovic M, Spencer SP. 241.  et al. 2014. Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis. Science 343:1249288 [Google Scholar]
  242. Muhl H. 242.  2013. Pro-inflammatory signaling by IL-10 and IL-22: bad habit stirred up by interferons?. Front. Immunol. 4:18 [Google Scholar]
  243. Nagalakshmi ML, Rascle A, Zurawski S, Menon S, de Waal Malefyt R. 243.  2004. Interleukin-22 activates STAT3 and induces IL-10 by colon epithelial cells. Int. Immunopharmacol. 4:679–91 [Google Scholar]
  244. Hosokawa Y, Hosokawa I, Shindo S, Ozaki K, Matsuo T. 244.  2014. IL-22 enhances CCL20 production in IL-1β-stimulated human gingival fibroblasts. Inflammation 37:2062–66 [Google Scholar]
  245. Rabeony H, Petit-Paris I, Garnier J, Barrault C, Pedretti N. 245.  et al. 2014. Inhibition of keratinocyte differentiation by the synergistic effect of IL-17A, IL-22, IL-1α, TNFα and oncostatin M. PLOS ONE 9:e101937 [Google Scholar]
  246. Sonnenberg GF. 246.  2010. Pathological versus protective functions of IL-22 in airway inflammation are regulated by IL-17A. J. Exp. Med. 207:1293–305 [Google Scholar]
  247. Zhao J, Zhang Z, Luan Y, Zou Z, Sun Y. 247.  et al. 2014. Pathological functions of interleukin-22 in chronic liver inflammation and fibrosis with hepatitis B virus infection by promoting T helper 17 cell recruitment. Hepatology 59:1331–42 [Google Scholar]
  248. Eken A, Singh AK, Treuting PM, Oukka M. 248.  2014. IL-23R+ innate lymphoid cells induce colitis via interleukin-22-dependent mechanism. Mucosal Immunol. 7:143–54 [Google Scholar]
  249. Uhlig HH, McKenzie BS, Hue S, Thompson C, Joyce-Shaikh B. 249.  et al. 2006. Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity 25:309–18 [Google Scholar]
  250. Souza JM, Matias BF, Rodrigues CM, Murta EF, Michelin MA. 250.  2013. IL-17 and IL-22 serum cytokine levels in patients with squamous intraepithelial lesion and invasive cervical carcinoma. Eur. J. Gynaecol. Oncol. 34:466–68 [Google Scholar]
  251. Schmechel S, Konrad A, Diegelmann J, Glas J, Wetzke M. 251.  et al. 2008. Linking genetic susceptibility to Crohn's disease with Th17 cell function: IL-22 serum levels are increased in Crohn's disease and correlate with disease activity and IL23R genotype status. Inflamm. Bowel Dis. 14:204–12 [Google Scholar]
  252. Liang SC, Nickerson-Nutter C, Pittman DD, Carrier Y, Goodwin DG. 252.  et al. 2010. IL-22 induces an acute-phase response. J. Immunol. 185:5531–38 [Google Scholar]
  253. Ciccia F, Guggino G, Rizzo A, Ferrante A, Raimondo S. 253.  et al. 2012. Potential involvement of IL-22 and IL-22-producing cells in the inflamed salivary glands of patients with Sjogren's syndrome. Ann. Rheum. Dis. 71:295–301 [Google Scholar]
  254. Delsing CE, Bleeker-Rovers CP, van de Veerdonk FL, Tol J, van der Meer JW. 254.  et al. 2012. Association of esophageal candidiasis and squamous cell carcinoma. Med. Mycol. Case Rep. 1:5–8 [Google Scholar]
  255. Hughes T, Becknell B, McClory S, Briercheck E, Freud AG. 255.  et al. 2009. Stage 3 immature human natural killer cells found in secondary lymphoid tissue constitutively and selectively express the TH17 cytokine interleukin-22. Blood 113:4008–10 [Google Scholar]
  256. Kato-Kogoe N, Nishioka T, Kawabe M, Kataoka F, Yamanegi K. 256.  et al. 2012. The promotional effect of IL-22 on mineralization activity of periodontal ligament cells. Cytokine 59:41–48 [Google Scholar]
  257. Naher L, Kiyoshima T, Kobayashi I, Wada H, Nagata K. 257.  et al. 2012. STAT3 signal transduction through interleukin-22 in oral squamous cell carcinoma. Int. J. Oncol. 41:1577–86 [Google Scholar]
  258. Zhuang Y. 258.  2012. Increased intratumoral IL-22-producing CD4+ T cells and Th22 cells correlate with gastric cancer progression and predict poor patient survival. Cancer Immunol. Immunother. 61:1965–75 [Google Scholar]
  259. te Velde AA, de Kort F, Sterrenburg E, Pronk I, ten Kate FJ. 259.  et al. 2007. Comparative analysis of colonic gene expression of three experimental colitis models mimicking inflammatory bowel disease. Inflamm. Bowel Dis. 13:325–30 [Google Scholar]
  260. Sadighi Akha AA, Theriot CM, Erb-Downward JR, McDermott AJ, Falkowski NR. 260.  et al. 2013. Acute infection of mice with Clostridium difficile leads to eIF2α phosphorylation and pro-survival signalling as part of the mucosal inflammatory response. Immunology 140:111–22 [Google Scholar]
  261. Bishop JL, Roberts ME, Beer JL, Huang M, Chehal MK. 261.  et al. 2014. Lyn activity protects mice from DSS colitis and regulates the production of IL-22 from innate lymphoid cells. Mucosal Immunol. 7:405–16 [Google Scholar]
  262. Sonnenberg GF, Monticelli LA, Alenghat T, Fung TC, Hutnick NA. 262.  et al. 2012. Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria. Science 336:1321–25 [Google Scholar]
  263. Sawa S, Lochner M, Satoh-Takayama N, Dulauroy S, Berard M. 263.  et al. 2011. RORγt+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota. Nat. Immunol. 12:320–26 [Google Scholar]
  264. Pickert G, Neufert C, Leppkes M, Zheng Y, Wittkopf N. 264.  et al. 2009. STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing. J. Exp. Med. 206:1465–72 [Google Scholar]
  265. Kim CJ. 265.  2012. A role for mucosal IL-22 production and Th22 cells in HIV-associated mucosal immunopathogenesis. Mucosal Immunol. 5:670–80 [Google Scholar]
  266. Mizuno S, Mikami Y, Kamada N, Handa T, Hayashi A. 266.  et al. 2014. Cross-talk between RORγt+ innate lymphoid cells and intestinal macrophages induces mucosal IL-22 production in Crohn's disease. Inflamm. Bowel Dis. 20:1426–34 [Google Scholar]
  267. Sanos SL, Vonarbourg C, Mortha A, Diefenbach A. 267.  2011. Control of epithelial cell function by interleukin-22-producing RORγt+ innate lymphoid cells. Immunology 132:453–65 [Google Scholar]
  268. Konieczna P, Ferstl R, Ziegler M, Frei R, Nehrbass D. 268.  et al. 2013. Immunomodulation by Bifidobacterium infantis 35624 in the murine lamina propria requires retinoic acid-dependent and independent mechanisms. PLOS ONE 8:e62617 [Google Scholar]
  269. Peterson LW, Artis D. 269.  2014. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat. Rev. Immunol. 14:141–53 [Google Scholar]
  270. Salzman NH, Bevins CL. 270.  2013. Dysbiosis—a consequence of Paneth cell dysfunction. Semin. Immunol. 25:334–41 [Google Scholar]
  271. Kolls JK, McCray PB Jr, Chan YR. 271.  2008. Cytokine-mediated regulation of antimicrobial proteins. Nat. Rev. Immunol. 8:829–35 [Google Scholar]
  272. Burger-van Paassen N, Loonen LM, Witte-Bouma J, Korteland-van Male AM, de Bruijn AC. 272.  et al. 2012. Mucin Muc2 deficiency and weaning influences the expression of the innate defense genes Reg3β, Reg3γ and angiogenin-4. PLOS ONE 7:e38798 [Google Scholar]
  273. Eriguchi Y, Uryu H, Nakamura K, Shimoji S, Takashima S. 273.  et al. 2013. Reciprocal expression of enteric antimicrobial proteins in intestinal graft-versus-host disease. Biol. Blood Marrow Transplant. 19:1525–29 [Google Scholar]
  274. Reynders A, Yessaad N, Manh TPV, Dalod M, Fenis A. 274.  et al. 2011. Identity, regulation and in vivo function of gut NKp46+RORγt+ and NKp46+RORγt lymphoid cells. EMBO J. 30:2934–47 [Google Scholar]
  275. Eberl G, Sawa S. 275.  2010. Opening the crypt: current facts and hypotheses on the function of cryptopatches. Trends Immunol. 31:50–55 [Google Scholar]
  276. Kanamori Y, Ishimaru K, Nanno M, Maki K, Ikuta K. 276.  et al. 1996. Identification of novel lymphoid tissues in murine intestinal mucosa where clusters of c-kit+IL-7R+Thy1+ lympho-hemopoietic progenitors develop. J. Exp. Med. 184:1449–59 [Google Scholar]
  277. Fagarasan S, Muramatsu M, Suzuki K, Nagaoka H, Hiai H, Honjo T. 277.  2002. Critical roles of activation-induced cytidine deaminase in the homeostasis of gut flora. Science 298:1424–27 [Google Scholar]
  278. Lorenz RG, Newberry RD. 278.  2004. Isolated lymphoid follicles can function as sites for induction of mucosal immune responses. Ann. N.Y. Acad. Sci. 1029:44–57 [Google Scholar]
  279. Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R. 279.  2004. IL-22 increases the innate immunity of tissues. Immunity 21:241–54 [Google Scholar]
  280. Wolk K, Witte E, Wallace E, Docke WD, Kunz S. 280.  et al. 2006. IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur. J. Immunol. 36:1309–23 [Google Scholar]
  281. Boniface K. 281.  2005. IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes. J. Immunol. 174:3695–702 [Google Scholar]
  282. Wolk K. 282.  2009. IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-γ are not. J. Mol. Med. 87:523–36 [Google Scholar]
  283. Sa SM. 283.  2007. The effects of IL-20 subfamily cytokines on reconstituted human epidermis suggest potential roles in cutaneous innate defense and pathogenic adaptive immunity in psoriasis. J. Immunol. 178:2229–40 [Google Scholar]
  284. Wolk K. 284.  2009. The Th17 cytokine IL-22 induces IL-20 production in keratinocytes: a novel immunological cascade with potential relevance in psoriasis. Eur. J. Immunol. 39:3570–81 [Google Scholar]
  285. Romer J. 285.  2003. Epidermal overexpression of interleukin-19 and -20 mRNA in psoriatic skin disappears after short-term treatment with cyclosporine A or calcipotriol. J. Investig. Dermatol. 121:1306–11 [Google Scholar]
  286. Kunz S. 286.  2006. Interleukin (IL)-19, IL-20 and IL-24 are produced by and act on keratinocytes and are distinct from classical ILs. Exp. Dermatol. 15:991–1004 [Google Scholar]
  287. Nestle FO, Kaplan DH, Barker J. 287.  2009. Psoriasis. N. Engl. J. Med. 361:496–509 [Google Scholar]
  288. Lowes MA, Suarez-Farinas M, Krueger JG. 288.  2014. Immunology of psoriasis. Annu. Rev. Immunol. 32:227–55 [Google Scholar]
  289. Saeki H, Hirota T, Nakagawa H, Tsunemi Y, Kato T. 289.  et al. 2013. Genetic polymorphisms in the IL22 gene are associated with psoriasis vulgaris in a Japanese population. J. Dermatol. Sci. 71:148–50 [Google Scholar]
  290. Nikamo P, Cheuk S, Lysell J, Enerback C, Bergh K. 290.  et al. 2014. Genetic variants of the IL22 promoter associate to onset of psoriasis before puberty and increased IL-22 production in T cells. J. Investig. Dermatol. 134:1535–41 [Google Scholar]
  291. Prans E, Kingo K, Traks T, Silm H, Vasar E, Koks S. 291.  2013. Copy number variations in IL22 gene are associated with Psoriasis vulgaris. Hum. Immunol. 74:792–95 [Google Scholar]
  292. Johnston A, Gudjonsson JE. 292.  2014. 22 again: IL-22 as a risk gene and important mediator in psoriasis. J. Investig. Dermatol. 134:1501–3 [Google Scholar]
  293. Boniface K, Guignouard E, Pedretti N, Garcia M, Delwail A. 293.  et al. 2007. A role for T cell-derived interleukin 22 in psoriatic skin inflammation. Clin. Exp. Immunol. 150:407–15 [Google Scholar]
  294. Lo YH, Torii K, Saito C, Furuhashi T, Maeda A, Morita A. 294.  2010. Serum IL-22 correlates with psoriatic severity and serum IL-6 correlates with susceptibility to phototherapy. J. Dermatol. Sci. 58:225–27 [Google Scholar]
  295. Shimauchi T, Hirakawa S, Suzuki T, Yasuma A, Majima Y. 295.  et al. 2013. Serum interleukin-22 and vascular endothelial growth factor serve as sensitive biomarkers but not as predictors of therapeutic response to biologics in patients with psoriasis. J. Dermatol. 40:805–12 [Google Scholar]
  296. Blumberg H. 296.  2001. Interleukin 20: discovery, receptor identification, and role in epidermal function. Cell 104:9–19 [Google Scholar]
  297. Stenderup K. 297.  2009. Interleukin-20 plays a critical role in maintenance and development of psoriasis in the human xenograft transplantation model. Br. J. Dermatol. 160:284–96 [Google Scholar]
  298. Teunissen MB, Munneke JM, Bernink JH, Spuls PI, Res PC. 298.  et al. 2014. Composition of innate lymphoid cell subsets in the human skin: enrichment of NCR ILC3 in lesional skin and blood of psoriasis patients. J. Investig. Dermatol. 134:2351–60 [Google Scholar]
  299. Villanova F, Flutter B, Tosi I, Grys K, Sreeneebus H. 299.  et al. 2014. Characterization of innate lymphoid cells in human skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis. J. Investig. Dermatol. 134:984–91 [Google Scholar]
  300. Dyring-Andersen B, Geisler C, Agerbeck C, Lauritsen JP, Gudjonsdottir SD. 300.  et al. 2014. Increased number and frequency of group 3 innate lymphoid cells in nonlesional psoriatic skin. Br. J. Dermatol. 170:609–16 [Google Scholar]
  301. Perera GK, Ainali C, Semenova E, Hundhausen C, Barinaga G. 301.  et al. 2014. Integrative biology approach identifies cytokine targeting strategies for psoriasis. Sci. Transl. Med. 6:223ra22 [Google Scholar]
  302. Ma HL. 302.  2008. IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation. J. Clin. Investig. 118:597–607 [Google Scholar]
  303. 303. ClinicalTrials.gov 2011. Study evaluating single dose of ILV-095 in psoriasis subjects Study identifier NCT01010542, Natl. Libr. Med., Bethesda, MD. Last updated July 5. http://clinicaltrials.gov/show/NCT01010542
  304. 304. ClinicalTrials.gov 2014. A randomized placebo-controlled study to determine the safety, tolerability, pharmacodynamics and clinical efficacy of ILV-094(an IL-22 antibody) administered intravenously to subjects with atopic dermatitis (AD) Study identifier NCT01941537, Natl. Libr. Med., Bethesda, MD. Last updated Feb. 11. http://clinicaltrials.gov/show/NCT01941537 [Google Scholar]
  305. McAleer JP, Kolls JK. 305.  2014. Directing traffic: IL-17 and IL-22 coordinate pulmonary immune defense. Immunol. Rev. 260:129–44 [Google Scholar]
  306. Chen K, Pociask DA, McAleer JP, Chan YR, Alcorn JF. 306.  et al. 2011. IL-17RA is required for CCL2 expression, macrophage recruitment, and emphysema in response to cigarette smoke. PLOS ONE 6:e20333 [Google Scholar]
  307. Besnard AG. 307.  2011. Dual role of IL-22 in allergic airway inflammation and its cross-talk with IL-17A. Am. J. Respir. Crit. Care Med. 183:1153–63 [Google Scholar]
  308. Farfariello V. 308.  2011. IL-22 mRNA in peripheral blood mononuclear cells from allergic rhinitic and asthmatic pediatric patients. Pediatr. Allergy Immunol. 22:419–23 [Google Scholar]
  309. Takahashi K. 309.  2011. IL-22 attenuates IL-25 production by lung epithelial cells and inhibits antigen-induced eosinophilic airway inflammation. J. Allergy Clin. Immunol. 128:1067–76 [Google Scholar]
  310. Nakagome K. 310.  2011. High expression of IL-22 suppresses antigen-induced immune responses and eosinophilic airway inflammation via an IL-10-associated mechanism. J. Immunol. 187:5077–89 [Google Scholar]
  311. Taube C. 311.  2011. IL-22 is produced by innate lymphoid cells and limits inflammation in allergic airway disease. PLOS ONE 6:e21799 [Google Scholar]
  312. Van Maele L, Carnoy C, Cayet D, Ivanov S, Porte R. 312.  et al. 2014. Activation of type 3 innate lymphoid cells and interleukin 22 secretion in the lungs during Streptococcus pneumoniae infection. J. Infect. Dis. 210:493–503 [Google Scholar]
  313. Xu X, Weiss ID, Zhang HH, Singh SP, Wynn TA. 313.  et al. 2014. Conventional NK cells can produce IL-22 and promote host defense in Klebsiella pneumoniae pneumonia. J. Immunol. 192:1778–86 [Google Scholar]
  314. Peng Y, Gao X, Yang J, Shekhar S, Wang S. 314.  et al. 2014. IL-22 Promotes Th1/Th17 immunity in chlamydial lung infection. Mol. Med. 20:109–19 [Google Scholar]
  315. Gessner MA. 315.  2012. Dectin-1-dependent interleukin-22 contributes to early innate lung defense against Aspergillus fumigatus. Infect. Immun. 80:410–17 [Google Scholar]
  316. Gresnigt MS, Becker KL, Smeekens SP, Jacobs CW, Joosten LA. 316.  et al. 2013. Aspergillus fumigatus-induced IL-22 is not restricted to a specific Th cell subset and is dependent on complement receptor 3. J. Immunol. 190:5629–39 [Google Scholar]
  317. Lilly LM, Gessner MA, Dunaway CW, Metz AE, Schwiebert L. 317.  et al. 2012. The β-glucan receptor dectin-1 promotes lung immunopathology during fungal allergy via IL-22. J. Immunol. 189:3653–60 [Google Scholar]
  318. Mear JB, Gosset P, Kipnis E, Faure E, Dessein R. 318.  et al. 2014. Candida albicans airway exposure primes the lung innate immune response against Pseudomonas aeruginosa infection through innate lymphoid cell recruitment and interleukin-22-associated mucosal response. Infect. Immun. 82:306–15 [Google Scholar]
  319. Kumar P, Thakar MS, Ouyang W, Malarkannan S. 319.  2013. IL-22 from conventional NK cells is epithelial regenerative and inflammation protective during influenza infection. Mucosal Immunol. 6:69–82 [Google Scholar]
  320. Guo H, Topham DJ. 320.  2010. Interleukin-22 (IL-22) production by pulmonary natural killer cells and the potential role of IL-22 during primary influenza virus infection. J. Virol. 84:7750–59 [Google Scholar]
  321. Pociask DA. 321.  2013. IL-22 is essential for lung epithelial repair following influenza infection. Am. J. Pathol. 182:1286–96 [Google Scholar]
  322. Ivanov S. 322.  2013. Interleukin-22 reduces lung inflammation during influenza A virus infection and protects against secondary bacterial infection. J. Virol. 87:6911–24 [Google Scholar]
  323. Simonian PL. 323.  2010. γδ T cells protect against lung fibrosis via IL-22. J. Exp. Med. 207:2239–53 [Google Scholar]
  324. Hoegl S. 324.  2011. Protective properties of inhaled IL-22 in a model of ventilator-induced lung injury. Am. J. Respir. Cell. Mol. Biol. 44:369–76 [Google Scholar]
  325. Yao S, Huang D, Chen CY, Halliday L, Zeng G. 325.  et al. 2010. Differentiation, distribution and γδ T cell-driven regulation of IL-22-producing T cells in tuberculosis. PLOS Pathog. 6:e1000789 [Google Scholar]
  326. Lutay N, Hakansson G, Alaridah N, Hallgren O, Westergren-Thorsson G, Godaly G. 326.  2014. Mycobacteria bypass mucosal NF-kB signalling to induce an epithelial anti-inflammatory IL-22 and IL-10 response. PLOS ONE 9:e86466 [Google Scholar]
  327. Dhiman R, Periasamy S, Barnes PF, Jaiswal AG, Paidipally P. 327.  et al. 2012. NK1.1+ cells and IL-22 regulate vaccine-induced protective immunity against challenge with Mycobacterium tuberculosis. J. Immunol. 189:897–905 [Google Scholar]
  328. Zhang Y. 328.  2011. A proinflammatory role for interleukin-22 in the immune response to hepatitis B virus. Gastroenterology 141:1897–906 [Google Scholar]
  329. Pan H, Hong F, Radaeva S, Gao B. 329.  2004. Hydrodynamic gene delivery of interleukin-22 protects the mouse liver from concanavalin A-, carbon tetrachloride-, and Fas ligand-induced injury via activation of STAT3. Cell. Mol. Immunol. 1:43–49 [Google Scholar]
  330. Radaeva S, Sun R, Pan HN, Hong F, Gao B. 330.  2004. Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation. Hepatology 39:1332–42 [Google Scholar]
  331. Zenewicz LA. 331.  2007. Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation. Immunity 27:647–59 [Google Scholar]
  332. Park O. 332.  2011. In vivo consequences of liver-specific interleukin-22 expression in mice: implications for human liver disease progression. Hepatology 54:252–61 [Google Scholar]
  333. Ki SH. 333.  2010. Interleukin-22 treatment ameliorates alcoholic liver injury in a murine model of chronic-binge ethanol feeding: role of signal transducer and activator of transcription 3. Hepatology 52:1291–300 [Google Scholar]
  334. Schulz SM. 334.  2008. Protective immunity to systemic infection with attenuated Salmonella enterica serovar enteritidis in the absence of IL-12 is associated with IL-23-dependent IL-22, but not IL-17. J. Immunol. 181:7891–901 [Google Scholar]
  335. Chestovich PJ. 335.  2012. Interleukin-22: implications for liver ischemia-reperfusion injury. Transplantation 93:485–92 [Google Scholar]
  336. Mastelic B. 336.  2012. IL-22 protects against liver pathology and lethality of an experimental blood-stage malaria infection. Front. Immunol. 3:85 [Google Scholar]
  337. Feng D. 337.  2012. Interleukin-22 promotes proliferation of liver stem/progenitor cells in mice and patients with chronic hepatitis B virus infection. Gastroenterology 143:188–98 [Google Scholar]
  338. Ren X, Hu B, Colletti LM. 338.  2010. IL-22 is involved in liver regeneration after hepatectomy. Am. J. Physiol. Gastrointest. Liver Physiol. 298:G74–80 [Google Scholar]
  339. Dambacher J. 339.  2008. The role of interleukin-22 in hepatitis C virus infection. Cytokine 41:209–16 [Google Scholar]
  340. Aggarwal S, Xie MH, Maruoka M, Foster J, Gurney AL. 340.  2001. Acinar cells of the pancreas are a target of interleukin-22. J. Interferon Cytokine Res. 21:1047–53 [Google Scholar]
  341. Tachiiri A, Imamura R, Wang Y, Fukui M, Umemura M, Suda T. 341.  2003. Genomic structure and inducible expression of the IL-22 receptor α chain in mice. Genes Immun. 4:153–59 [Google Scholar]
  342. Kulkarni OP, Hartter I, Mulay SR, Hagemann J, Darisipudi MN. 342.  et al. 2014. Toll-like receptor 4-induced IL-22 accelerates kidney regeneration. J. Am. Soc. Nephrol. 25:978–89 [Google Scholar]
  343. Weber GF, Schlautkotter S, Kaiser-Moore S, Altmayr F, Holzmann B, Weighardt H. 343.  2007. Inhibition of interleukin-22 attenuates bacterial load and organ failure during acute polymicrobial sepsis. Infect. Immun. 75:1690–97 [Google Scholar]
  344. Zhang F, Shang D, Zhang Y, Tian Y. 344.  2011. Interleukin-22 suppresses the growth of A498 renal cell carcinoma cells via regulation of STAT1 pathway. PLOS ONE 6:e20382 [Google Scholar]
  345. Suh JS, Cho SH, Chung JH, Moon A, Park YK, Cho BS. 345.  2013. A polymorphism of interleukin-22 receptor α-1 is associated with the development of childhood IgA nephropathy. J. Interferon Cytokine Res. 33:571–77 [Google Scholar]
  346. Parrish-Novak J, Xu W, Brender T, Yao L, Jones C. 346.  et al. 2002. Interleukins 19, 20, and 24 signal through two distinct receptor complexes. Differences in receptor-ligand interactions mediate unique biological functions. J. Biol. Chem. 277:47517–23 [Google Scholar]
  347. Shioya M, Andoh A, Kakinoki S, Nishida A, Fujiyama Y. 347.  2008. Interleukin 22 receptor 1 expression in pancreas islets. Pancreas 36:197–99 [Google Scholar]
  348. Xue J, Nguyen DT, Habtezion A. 348.  2012. Aryl hydrocarbon receptor regulates pancreatic IL-22 production and protects mice from acute pancreatitis. Gastroenterology 143:1670–80 [Google Scholar]
  349. Hill T. 349.  2013. The involvement of interleukin-22 in the expression of pancreatic β cell regenerative Reg genes. Cell Regener. 2:2 [Google Scholar]
  350. Feng D. 350.  2012. Interleukin-22 ameliorates cerulein-induced pancreatitis in mice by inhibiting the autophagic pathway. Int. J. Biol. Sci. 8:249–57 [Google Scholar]
  351. Lo Re S. 351.  2010. IL-17A-producing γδ T and Th17 lymphocytes mediate lung inflammation but not fibrosis in experimental silicosis. J. Immunol. 184:6367–77 [Google Scholar]
  352. Shen H, Goodall JC, Hill Gaston JS. 352.  2009. Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis Rheum. 60:1647–56 [Google Scholar]
  353. Leipe J. 353.  2011. Interleukin 22 serum levels are associated with radiographic progression in rheumatoid arthritis. Ann. Rheum. Dis. 70:1453–57 [Google Scholar]
  354. Zhang L. 354.  2011. Elevated Th22 cells correlated with Th17 cells in patients with rheumatoid arthritis. J. Clin. Immunol. 31:606–14 [Google Scholar]
  355. da Rocha LF Jr. 355.  2012. Increased serum interleukin 22 in patients with rheumatoid arthritis and correlation with disease activity. J. Rheumatol 39:1320–25 [Google Scholar]
  356. Kim KW. 356.  2012. Interleukin-22 promotes osteoclastogenesis in rheumatoid arthritis through induction of RANKL in human synovial fibroblasts. Arthritis Rheum. 64:1015–23 [Google Scholar]
  357. Kim K, Kim G, Kim JY, Yun HJ, Lim SC, Choi HS. 357.  2014. Interleukin-22 promotes epithelial cell transformation and breast tumorigenesis via MAP3K8 activation. Carcinogenesis 35:1352–61 [Google Scholar]
  358. Kryczek I, Lin Y, Nagarsheth N, Peng D, Zhao L. 358.  et al. 2014. IL-22+CD4+ T cells promote colorectal cancer stemness via STAT3 transcription factor activation and induction of the methyltransferase DOT1L. Immunity 40:772–84 [Google Scholar]
  359. Fukui H, Zhang X, Sun C, Hara K, Kikuchi S. 359.  et al. 2014. IL-22 produced by cancer-associated fibroblasts promotes gastric cancer cell invasion via STAT3 and ERK signaling. Br. J. Cancer 111:763–71 [Google Scholar]
  360. Liu F, Pan X, Zhou L, Zhou J, Chen B. 360.  et al. 2014. Genetic polymorphisms and plasma levels of interleukin-22 contribute to the development of nonsmall cell lung cancer. DNA Cell Biol. 33:705–14 [Google Scholar]
  361. Qin S, Ma S, Huang X, Lu D, Zhou Y, Jiang H. 361.  2014. Th22 cells are associated with hepatocellular carcinoma development and progression. Chin. J. Cancer Res. 26:135–41 [Google Scholar]
  362. Wen Z, Liao Q, Zhao J, Hu Y, You L. 362.  et al. 2014. High expression of interleukin-22 and its receptor predicts poor prognosis in pancreatic ductal adenocarcinoma. Ann. Surg. Oncol. 21:125–32 [Google Scholar]
  363. Jiang R, Zhang C, Xia Y, Qian X, Wang X, Sun B. 363.  2014. Reply: To PMID 21674558. Hepatology 59:1208 [Google Scholar]
  364. Waidmann O, Kronenberger B, Scheiermann P, Koberle V, Muhl H, Piiper A. 364.  2014. Interleukin-22 serum levels are a negative prognostic indicator in patients with hepatocellular carcinoma. Hepatology 59:1207 [Google Scholar]
  365. Kobold S. 365.  2013. Interleukin-22 is frequently expressed in small- and large-cell lung cancer and promotes growth in chemotherapy-resistant cancer cells. J. Thorac. Oncol. 8:1032–42 [Google Scholar]
  366. Zhang S, Fujita H, Mitsui H, Yanofsky VR, Fuentes-Duculan J. 366.  et al. 2013. Increased Tc22 and Treg/CD8 ratio contribute to aggressive growth of transplant associated squamous cell carcinoma. PLOS ONE 8:e62154 [Google Scholar]
  367. Eun YG, Shin IH, Lee YC, Shin SY, Kim SK. 367.  et al. 2013. Interleukin 22 polymorphisms and papillary thyroid cancer. J. Endocrinol. Investig. 36:584–7 [Google Scholar]
  368. Kirchberger S, Royston DJ, Boulard O, Thornton E, Franchini F. 368.  et al. 2013. Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model. J. Exp. Med. 210:917–31 [Google Scholar]
  369. Zhao K, Zhao D, Huang D, Song X, Chen C. 369.  et al. 2013. The identification and characteristics of IL-22-producing T cells in acute graft-versus-host disease following allogeneic bone marrow transplantation. Immunobiology 218:1505–13 [Google Scholar]
  370. Couturier M, Lamarthee B, Arbez J, Renauld JC, Bossard C. 370.  et al. 2013. IL-22 deficiency in donor T cells attenuates murine acute graft-versus-host disease mortality while sparing the graft-versus-leukemia effect. Leukemia 27:1527–37 [Google Scholar]
  371. Zhao K, Zhao D, Huang D, Yin L, Chen C. 371.  et al. 2014. Interleukin-22 aggravates murine acute graft-versus-host disease by expanding effector T cell and reducing regulatory T cell. J. Interferon Cytokine Res. 34:707–15 [Google Scholar]
  372. Munneke JM, Bjorklund AT, Mjosberg JM, Garming-Legert K, Bernink JH. 372.  et al. 2014. Activated innate lymphoid cells are associated with a reduced susceptibility to graft-versus-host disease. Blood 124:812–21 [Google Scholar]
  373. Bruggen MC, Klein I, Greinix H, Bauer W, Kuzmina Z. 373.  et al. 2014. Diverse T-cell responses characterize the different manifestations of cutaneous graft-versus-host disease. Blood 123:290–99 [Google Scholar]
  374. Laakso SM, Kekalainen E, Heikkila N, Mannerstrom H, Kisand K. 374.  et al. 2014. In vivo analysis of helper T cell responses in patients with autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy provides evidence in support of an IL-22 defect. Autoimmunity 47:556–62 [Google Scholar]
  375. Karner J, Meager A, Laan M, Maslovskaja J, Pihlap M. 375.  et al. 2013. Anti-cytokine autoantibodies suggest pathogenetic links with autoimmune regulator deficiency in humans and mice. Clin. Exp. Immunol. 171:263–72 [Google Scholar]
  376. Leung JM, Davenport M, Wolff MJ, Wiens KE, Abidi WM. 376.  et al. 2014. IL-22-producing CD4+ cells are depleted in actively inflamed colitis tissue. Mucosal Immunol. 7:124–33 [Google Scholar]
  377. Xu H, Feely SL, Wang X, Liu DX, Borda JT. 377.  et al. 2013. Gluten-sensitive enteropathy coincides with decreased capability of intestinal T cells to secrete IL-17 and IL-22 in a macaque model for celiac disease. Clin. Immunol. 147:40–49 [Google Scholar]
  378. Hollander GA, Krenger W, Blazar BR. 378.  2010. Emerging strategies to boost thymic function. Curr. Opin. Pharmacol. 10:443–53 [Google Scholar]
  379. Boehm T, Swann JB. 379.  2013. Thymus involution and regeneration: two sides of the same coin?. Nat. Rev. Immunol. 13:831–38 [Google Scholar]
  380. Legrand N, Dontje W, van Lent AU, Spits H, Blom B. 380.  2007. Human thymus regeneration and T cell reconstitution. Semin. Immunol. 19:280–88 [Google Scholar]
  381. Maury S, Mary JY, Rabian C, Schwarzinger M, Toubert A. 381.  et al. 2001. Prolonged immune deficiency following allogeneic stem cell transplantation: risk factors and complications in adult patients. Br. J. Haematol. 115:630–41 [Google Scholar]
  382. Storek J, Gooley T, Witherspoon RP, Sullivan KM, Storb R. 382.  1997. Infectious morbidity in long-term survivors of allogeneic marrow transplantation is associated with low CD4 T cell counts. Am. J. Hematol. 54:131–38 [Google Scholar]
  383. Maraninchi D, Gluckman E, Blaise D, Guyotat D, Rio B. 383.  et al. 1987. Impact of T-cell depletion on outcome of allogeneic bone-marrow transplantation for standard-risk leukaemias. Lancet 2:175–78 [Google Scholar]
  384. Curtis RE, Rowlings PA, Deeg HJ, Shriner DA, Socie G. 384.  et al. 1997. Solid cancers after bone marrow transplantation. N. Engl. J. Med. 336:897–904 [Google Scholar]
  385. Small TN, Papadopoulos EB, Boulad F, Black P, Castro-Malaspina H. 385.  et al. 1999. Comparison of immune reconstitution after unrelated and related T-cell-depleted bone marrow transplantation: effect of patient age and donor leukocyte infusions. Blood 93:467–80 [Google Scholar]
  386. Gray DH, Fletcher AL, Hammett M, Seach N, Ueno T. 386.  et al. 2008. Unbiased analysis, enrichment and purification of thymic stromal cells. J. Immunol. Methods 329:56–66 [Google Scholar]
  387. Pan B, Liu J, Zhang Y, Sun Y, Wu Q. 387.  et al. 2014. Acute ablation of DP thymocytes induces up-regulation of IL-22 and Foxn1 in TECs. Clin. Immunol. 150:101–8 [Google Scholar]
  388. Nehls M, Kyewski B, Messerle M, Waldschutz R, Schuddekopf K. 388.  et al. 1996. Two genetically separable steps in the differentiation of thymic epithelium. Science 272:886–89 [Google Scholar]
  389. Chen L, Xiao S, Manley NR. 389.  2009. Foxn1 is required to maintain the postnatal thymic microenvironment in a dosage-sensitive manner. Blood 113:567–74 [Google Scholar]
  390. Bleul CC, Corbeaux T, Reuter A, Fisch P, Monting JS, Boehm T. 390.  2006. Formation of a functional thymus initiated by a postnatal epithelial progenitor cell. Nature 441:992–96 [Google Scholar]
  391. Bredenkamp N, Nowell CS, Blackburn CC. 391.  2014. Regeneration of the aged thymus by a single transcription factor. Development 141:1627–37 [Google Scholar]
  392. Zook EC, Krishack PA, Zhang S, Zeleznik-Le NJ, Firulli AB. 392.  et al. 2011. Overexpression of Foxn1 attenuates age-associated thymic involution and prevents the expansion of peripheral CD4 memory T cells. Blood 118:5723–31 [Google Scholar]
  393. Hepworth MR, Monticelli LA, Fung TC, Ziegler CGK, Grunberg S. 393.  et al. 2013. Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria. Nature 498:113–17 [Google Scholar]
  394. Wilson MS. 394.  2010. Redundant and pathogenic roles for IL-22 in mycobacterial, protozoan, and helminth infections. J. Immunol. 184:4378–90 [Google Scholar]
  395. Graham AC. 395.  2011. IL-22 production is regulated by IL-23 during Listeria monocytogenes infection but is not required for bacterial clearance or tissue protection. PLOS ONE 6:e17171 [Google Scholar]
  396. Zenewicz LA. 396.  2013. IL-22 deficiency alters colonic microbiota to be transmissible and colitogenic. J. Immunol. 190:5306–12 [Google Scholar]
  397. De Luca A. 397.  2010. IL-22 defines a novel immune pathway of antifungal resistance. Mucosal Immunol. 3:361–73 [Google Scholar]
  398. Kisand K. 398.  2010. Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines. J. Exp. Med. 207:299–308 [Google Scholar]
  399. Zenewicz LA, Yancopoulos GD, Valenzuela DM, Murphy AJ, Karow M, Flavell RA. 399.  2007. Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation. Immunity 27:647–59 [Google Scholar]
/content/journals/10.1146/annurev-immunol-032414-112123
Loading
/content/journals/10.1146/annurev-immunol-032414-112123
Loading

Data & Media loading...

  • Article Type: Review Article