1932

Abstract

Professional antigen-presenting cells (APCs) in the skin include dendritic cells, monocytes, and macrophages. They are highly dynamic, with the capacity to enter skin from the peripheral circulation, patrol within tissue, and migrate through lymphatics to draining lymph nodes. Skin APCs are endowed with antigen-sensing, -processing, and -presenting machinery and play key roles in initiating, modulating, and resolving cutaneous inflammation. Skin APCs are a highly heterogeneous population with functionally specialized subsets that are developmentally imprinted and modulated by local tissue microenvironmental and inflammatory cues. This review explores recent advances that have allowed for a more accurate taxonomy of APC subsets found in both mouse and human skin. It also examines the functional specificity of individual APC subsets and their collaboration with other immune cell types that together promote adaptive T cell and regional cutaneous immune responses during homeostasis, inflammation, and disease.

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2017-04-26
2024-03-28
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Literature Cited

  1. Pasparakis M, Haase I, Nestle FO. 1.  2014. Mechanisms regulating skin immunity and inflammation. Nat. Rev. Immunol. 14:289–301 [Google Scholar]
  2. Langerhans P. 2.  1868. Ueber die Nerven der Menschlichen Haut. Arch. Pathol. Anat. Physiol. Klin. Med. 44:2–3325–37 [Google Scholar]
  3. Tauber AI. 3.  2003. Timeline: Metchnikoff and the phagocytosis theory. Nat. Rev. Mol. Cell Biol. 4:11897–901 [Google Scholar]
  4. Steinman RM, Cohn ZA. 4.  1973. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J. Exp. Med. 137:51142–62 [Google Scholar]
  5. Steinman RM, Cohn ZA. 5.  1974. Identification of a novel cell type in peripheral lymphoid organs of mice. II. Functional properties in vitro. J. Exp. Med. 139:2380–97 [Google Scholar]
  6. Silberberg-Sinakin I, Thorbecke GJ, Baer RL, Rosenthal SA, Berezowsky V. 6.  1976. Antigen-bearing Langerhans cells in skin, dermal lymphatics and in lymph nodes. Cell. Immunol. 25:2137–51 [Google Scholar]
  7. Stingl G, Wolff-Schreiner EC, Pichler WJ, Gschnait F, Knapp W, Wolff K. 7.  1977. Epidermal Langerhans cells bear Fc and C3 receptors. Nature 268:5617245–46 [Google Scholar]
  8. Rowden G, Lewis MG, Sullivan AK. 8.  1977. Ia antigen expression on human epidermal Langerhans cells. Nature 268:5617247–48 [Google Scholar]
  9. Klareskog L, Tjernlund U, Forsum U, Peterson PA. 9.  1977. Epidermal Langerhans cells express Ia antigens. Nature 268:5617248–50 [Google Scholar]
  10. Katz SI, Tamaki K, Sachs DH. 10.  1979. Epidermal Langerhans cells are derived from cells originating in bone marrow. Nature 282:5736324–26 [Google Scholar]
  11. Frelinger JA, Frelinger JG. 11.  1980. Bone marrow origin of Ia molecules purified from epidermal cells. J. Investig. Dermatol. 75:168–70 [Google Scholar]
  12. Lens JW, Drexhage HA, Benson W, Balfour BM. 12.  1983. A study of cells present in lymph draining from a contact allergic reaction in pigs sensitized to DNFB. Immunology 49:3415 [Google Scholar]
  13. Schuler G, Steinman RM. 13.  1985. Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J. Exp. Med. 161:3526–46 [Google Scholar]
  14. Nestle FO, Zheng XG, Thompson CB, Turka LA, Nickoloff BJ. 14.  1993. Characterization of dermal dendritic cells obtained from normal human skin reveals phenotypic and functionally distinctive subsets. J. Immunol. 151:116535–45 [Google Scholar]
  15. Lenz A, Heine M, Schuler G, Romani N. 15.  1993. Human and murine dermis contain dendritic cells. Isolation by means of a novel method and phenotypical and functional characterization. J. Clin. Investig. 92:62587–96 [Google Scholar]
  16. Merad M, Sathe P, Helft J, Miller J, Mortha A. 16.  2013. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu. Rev. Immunol. 31:563–604 [Google Scholar]
  17. Jakubzick C, Gautier EL, Gibbings SL, Sojka DK, Schlitzer A. 17.  et al. 2013. Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes. Immunity 39:3599–610 [Google Scholar]
  18. Tamoutounour S, Guilliams M, Montanana Sanchis F, Liu H, Terhorst D. 18.  et al. 2013. Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin. Immunity 39:5925–38 [Google Scholar]
  19. Haniffa M, Shin A, Bigley V, McGovern N, Teo P. 19.  et al. 2012. Human tissues contain CD141hi cross-presenting dendritic cells with functional homology to mouse CD103+ nonlymphoid dendritic cells. Immunity 37:160–73 [Google Scholar]
  20. van Furth R. 20.  1982. Current view on the mononuclear phagocyte system. Immunobiology 161:3–4178–85 [Google Scholar]
  21. Schlitzer A, Sivakamasundari V, Chen J, Sumatoh HRB, Schreuder J. 21.  et al. 2015. Identification of cDC1- and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow. Nat. Immunol. 16:7718–28 [Google Scholar]
  22. Ginhoux F, Jung S. 22.  2014. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat. Rev. Immunol. 14:6392–404 [Google Scholar]
  23. Lee J, Breton G, Oliveira TYK, Zhou YJ, Aljoufi A. 23.  et al. 2015. Restricted dendritic cell and monocyte progenitors in human cord blood and bone marrow. J. Exp. Med. 212:3385–99 [Google Scholar]
  24. Haniffa M, Bigley V, Collin M. 24.  2015. Human mononuclear phagocyte system reunited. Semin. Cell Dev. Biol. 41:59–69 [Google Scholar]
  25. de Jong A, Peña-Cruz V, Cheng T-Y, Clark RA, Van Rhijn I, Moody DB. 25.  2010. CD1a-autoreactive T cells are a normal component of the human αβ T cell repertoire. Nat. Immunol. 11:121102–9 [Google Scholar]
  26. Gordon S, Plüddemann A, Martinez Estrada F. 26.  2014. Macrophage heterogeneity in tissues: phenotypic diversity and functions. Immunol. Rev. 262:136–55 [Google Scholar]
  27. Abtin A, Jain R, Mitchell AJ, Roediger B, Brzoska AJ. 27.  et al. 2014. Perivascular macrophages mediate neutrophil recruitment during bacterial skin infection. Nat. Immunol. 15:145–53 [Google Scholar]
  28. Merad M, Ginhoux F, Collin M. 28.  2008. Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nat. Rev. Immunol. 8:12935–47 [Google Scholar]
  29. Kubo A, Nagao K, Yokouchi M, Sasaki H, Amagai M. 29.  2009. External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers. J. Exp. Med. 206:132937–46 [Google Scholar]
  30. Gaiser MR, Lämmermann T, Feng X, Igyarto BZ, Kaplan DH. 30.  et al. 2012. Cancer-associated epithelial cell adhesion molecule (EpCAM; CD326) enables epidermal Langerhans cell motility and migration in vivo. PNAS 109:15E889–97 [Google Scholar]
  31. Reynolds G, Haniffa M. 31.  2015. Human and mouse mononuclear phagocyte networks: a tale of two species?. Front. Immunol. 6:330 [Google Scholar]
  32. Schulz C, Gomez Perdiguero E, Chorro L, Szabo-Rogers H, Cagnard N. 32.  et al. 2012. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336:607786–90 [Google Scholar]
  33. Hoeffel G, Wang Y, Greter M, See P, Teo P. 33.  et al. 2012. Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. J. Exp. Med. 209:61167–81 [Google Scholar]
  34. Wang Y, Bugatti M, Ulland TK, Vermi W, Gilfillan S, Colonna M. 34.  2016. Nonredundant roles of keratinocyte-derived IL-34 and neutrophil-derived CSF1 in Langerhans cell renewal in the steady state and during inflammation. Eur. J. Immunol. 46:3552–59 [Google Scholar]
  35. Greter M, Lelios I, Pelczar P, Hoeffel G, Price J. 35.  et al. 2012. Stroma-derived interleukin-34 controls the development and maintenance of Langerhans cells and the maintenance of microglia. Immunity 37:61050–60 [Google Scholar]
  36. Wang Y, Szretter KJ, Vermi W, Gilfillan S, Rossini C. 36.  et al. 2012. IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nat. Immunol. 13:8753–60 [Google Scholar]
  37. Fainaru O, Woolf E, Lotem J, Yarmus M, Brenner O. 37.  et al. 2004. Runx3 regulates mouse TGF-β-mediated dendritic cell function and its absence results in airway inflammation. EMBO J 23:4969–79 [Google Scholar]
  38. Hacker C, Kirsch RD, Ju X-S, Hieronymus T, Gust TC. 38.  et al. 2003. Transcriptional profiling identifies Id2 function in dendritic cell development. Nat. Immunol. 4:4380–86 [Google Scholar]
  39. Yasmin N, Bauer T, Modak M, Wagner K, Schuster C. 39.  et al. 2013. Identification of bone morphogenetic protein 7 (BMP7) as an instructive factor for human epidermal Langerhans cell differentiation. J. Exp. Med. 210:122597–610 [Google Scholar]
  40. Kaplan DH, Li MO, Jenison MC, Shlomchik WD, Flavell RA, Shlomchik MJ. 40.  2007. Autocrine/paracrine TGFβ1 is required for the development of epidermal Langerhans cells. J. Exp. Med. 204:112545–52 [Google Scholar]
  41. Kel JM, Girard-Madoux MJH, Reizis B, Clausen BE. 41.  2010. TGF-β is required to maintain the pool of immature Langerhans cells in the epidermis. J. Immunol. 185:63248–55 [Google Scholar]
  42. Bobr A, Igyarto BZ, Haley KM, Li MO, Flavell RA, Kaplan DH. 42.  2012. Autocrine/paracrine TGF-β1 inhibits Langerhans cell migration. PNAS 109:10492–97 [Google Scholar]
  43. Mohammed J, Beura LK, Bobr A, Astry B, Chicoine B. 43.  et al. 2016. Stromal cells control the epithelial residence of DCs and memory T cells by regulated activation of TGF-β.. Nat. Immunol. 17:414–21 [Google Scholar]
  44. Hieronymus T, Zenke M, Baek J-H, Seré K. 44.  2015. The clash of Langerhans cell homeostasis in skin: Should I stay or should I go?. Semin. Cell Dev. Biol. 41:30–38 [Google Scholar]
  45. Milne P, Bigley V, Gunawan M, Haniffa M, Collin M. 45.  2015. CD1c+ blood dendritic cells have Langerhans cell potential. Blood 125:3470–73 [Google Scholar]
  46. Martinez-Cingolani C, Grandclaudon M, Jeanmougin M, Jouve M, Zollinger R, Soumelis V. 46.  2014. Human blood BDCA-1 dendritic cells differentiate into Langerhans-like cells with thymic stromal lymphopoietin and TGF-β.. Blood 124:152411–20 [Google Scholar]
  47. Merad M, Manz MG, Karsunky H, Wagers A, Peters W. 47.  et al. 2002. Langerhans cells renew in the skin throughout life under steady-state conditions. Nat. Immunol. 3:121135–41 [Google Scholar]
  48. Ghigo C, Mondor I, Jorquera A, Nowak J, Wienert S. 48.  et al. 2013. Multicolor fate mapping of Langerhans cell homeostasis. J. Exp. Med. 210:91657–64 [Google Scholar]
  49. Chorro L, Sarde A, Li M, Woollard KJ, Chambon P. 49.  et al. 2009. Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network. J. Exp. Med. 206:133089–100 [Google Scholar]
  50. Kanitakis J, Petruzzo P, Dubernard J-M. 50.  2004. Turnover of epidermal Langerhans’ cells. N. Engl. J. Med. 351:252661–62 [Google Scholar]
  51. Kanitakis J, Morelon E, Petruzzo P, Badet L, Dubernard J-M. 51.  2011. Self-renewal capacity of human epidermal Langerhans cells: observations made on a composite tissue allograft. Exp. Dermatol. 20:2145–46 [Google Scholar]
  52. Collin MP, Hart DNJ, Jackson GH, Cook G, Cavet J. 52.  et al. 2006. The fate of human Langerhans cells in hematopoietic stem cell transplantation. J. Exp. Med. 203:27 [Google Scholar]
  53. Price JG, Idoyaga J, Salmon H, Hogstad B, Bigarella CL. 53.  et al. 2015. CDKN1A regulates Langerhans cell survival and promotes Treg cell generation upon exposure to ionizing irradiation. Nat. Immunol. 16:101060–68 [Google Scholar]
  54. Ginhoux F, Tacke F, Angeli V, Bogunovic M, Loubeau M. 54.  et al. 2006. Langerhans cells arise from monocytes in vivo. Nat. Immunol. 7:3265–73 [Google Scholar]
  55. Seré K, Baek J-H, Ober-Blöbaum J, Müller-Newen G, Tacke F. 55.  et al. 2012. Two distinct types of Langerhans cells populate the skin during steady state and inflammation. Immunity 37:5905–16 [Google Scholar]
  56. Romani N, Schuler G, Fritsch P. 56.  1986. Ontogeny of Ia-positive and Thy-1-positive leukocytes of murine epidermis. J. Investig. Dermatol. 86:2129–33 [Google Scholar]
  57. Chang-Rodriguez S, Hoetzenecker W, Schwärzler C, Biedermann T, Saeland S, Elbe-Bürger A. 57.  2004. Fetal and neonatal murine skin harbors Langerhans cell precursors. J. Leukoc. Biol. 77:3352–60 [Google Scholar]
  58. Nagao K, Kobayashi T, Moro K, Ohyama M, Adachi T. 58.  et al. 2012. Stress-induced production of chemokines by hair follicles regulates the trafficking of dendritic cells in skin. Nat. Immunol. 13:8744–52 [Google Scholar]
  59. Lin H, Lee E, Hestir K, Leo C, Huang M. 59.  et al. 2008. Discovery of a cytokine and its receptor by functional screening of the extracellular proteome. Science 320:5877807–11 [Google Scholar]
  60. Wang Y, Szretter KJ, Vermi W, Gilfillan S, Rossini C. 60.  et al. 2012. IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nat. Immunol. 13:8753–60 [Google Scholar]
  61. Greter M, Lelios I, Pelczar P, Hoeffel G, Price J. 61.  et al. 2012. Stroma-derived interleukin-34 controls the development and maintenance of Langerhans cells and the maintenance of microglia. Immunity 37:61050–60 [Google Scholar]
  62. Ginhoux F, Liu K, Helft J, Bogunovic M, Greter M. 62.  et al. 2009. The origin and development of nonlymphoid tissue CD103+ DCs. J. Exp. Med. 206:133115–30 [Google Scholar]
  63. Guilliams M, Ginhoux F, Jakubzick C, Naik SH, Onai N. 63.  et al. 2014. Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat. Rev. Immunol. 14:8571–78 [Google Scholar]
  64. Gerner MY, Kastenmüller W, Ifrim I, Kabat J, Germain RN. 64.  2012. Histo-cytometry: a method for highly multiplex quantitative tissue imaging analysis applied to dendritic cell subset microanatomy in lymph nodes. Immunity 37:2364–76 [Google Scholar]
  65. Malissen B, Tamoutounour S, Henri S. 65.  2014. The origins and functions of dendritic cells and macrophages in the skin. Nat. Rev. Immunol. 14:6417–28 [Google Scholar]
  66. Dorner BG, Dorner MB, Zhou X, Opitz C, Mora A. 66.  et al. 2009. Selective expression of the chemokine receptor XCR1 on cross-presenting dendritic cells determines cooperation with CD8+ T cells. Immunity 31:5823–33 [Google Scholar]
  67. Zhang J-G, Czabotar PE, Policheni AN, Caminschi I, Wan SS. 67.  et al. 2012. The dendritic cell receptor Clec9A binds damaged cells via exposed actin filaments. Immunity 36:4646–57 [Google Scholar]
  68. Ahrens S, Zelenay S, Sancho D, Hanč P, Kjær S. 68.  et al. 2012. F-actin is an evolutionarily conserved damage-associated molecular pattern recognized by DNGR-1, a receptor for dead cells. Immunity 36:4635–45 [Google Scholar]
  69. Tamura T, Tailor P, Yamaoka K, Kong HJ, Tsujimura H. 69.  et al. 2005. IFN regulatory factor-4 and -8 govern dendritic cell subset development and their functional diversity. J. Immunol. 174:52573–81 [Google Scholar]
  70. Edelson BT, Wumesh KC, Juang R, Kohyama M, Benoit LA. 70.  et al. 2010. Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8α+ conventional dendritic cells. J. Exp. Med. 207:4823–36 [Google Scholar]
  71. Miller JC, Brown BD, Shay T, Gautier EL, Jojic V. 71.  et al. 2012. Deciphering the transcriptional network of the dendritic cell lineage. Nat. Immunol. 13:9888–99 [Google Scholar]
  72. Bursch LS, Wang L, Igyarto B, Kissenpfennig A, Malissen B. 72.  et al. 2007. Identification of a novel population of Langerin+ dendritic cells. J. Exp. Med. 204:133147–56 [Google Scholar]
  73. Waskow C, Liu K, Darrasse-Jèze G, Guermonprez P, Ginhoux F. 73.  et al. 2008. The receptor tyrosine kinase Flt3 is required for dendritic cell development in peripheral lymphoid tissues. Nat. Immunol. 9:6676–83 [Google Scholar]
  74. McKenna HJ, Stocking KL, Miller RE, Brasel K, De Smedt T. 74.  et al. 2000. Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells. Blood 95:113489–97 [Google Scholar]
  75. Hildner K, Hildner K, Edelson BT, Edelson BT, Purtha WE. 75.  et al. 2008. Batf3 deficiency reveals a critical role for CD8α+ dendritic cells in cytotoxic T cell immunity. Science 322:59041097–100 [Google Scholar]
  76. Poulin LF, Reyal Y, Uronen-Hansson H, Schraml BU, Sancho D. 76.  et al. 2012. DNGR-1 is a specific and universal marker of mouse and human Batf3-dependent dendritic cells in lymphoid and nonlymphoid tissues. Blood 119:256052–62 [Google Scholar]
  77. Balan S, Ollion V, Colletti N, Chelbi R, Montanana Sanchis F. 77.  et al. 2014. Human XCR1+ dendritic cells derived in vitro from CD34+ progenitors closely resemble blood dendritic cells, including their adjuvant responsiveness, contrary to monocyte-derived dendritic cells. J. Immunol. 193:41622–35 [Google Scholar]
  78. Hambleton S, Salem S, Bustamante J, Bigley V, Boisson-Dupuis S. 78.  et al. 2011. IRF8 mutations and human dendritic-cell immunodeficiency. N. Engl. J. Med. 365:2127–38 [Google Scholar]
  79. Tussiwand R, Lee W-L, Murphy TL, Mashayekhi M, Wumesh KC. 79.  et al. 2012. Compensatory dendritic cell development mediated by BATF-IRF interactions. Nature 490:502–7 [Google Scholar]
  80. Grajales-Reyes GE, Iwata A, Albring J, Wu X, Tussiwand R. 80.  et al. 2015. Batf3 maintains autoactivation of Irf8 for commitment of a CD8α+ conventional DC clonogenic progenitor. Nat. Immunol. 16:7708–17 [Google Scholar]
  81. Henri S, Poulin LF, Tamoutounour S, Ardouin L, Guilliams M. 81.  et al. 2010. CD207+ CD103+ dermal dendritic cells cross-present keratinocyte-derived antigens irrespective of the presence of Langerhans cells. J. Exp. Med. 207:1189–206 [Google Scholar]
  82. Vremec D, Shortman K. 82.  1997. Dendritic cell subtypes in mouse lymphoid organs: cross-correlation of surface markers, changes with incubation, and differences among thymus, spleen, and lymph nodes. J. Immunol. 159:2565–73 [Google Scholar]
  83. Shortman K, Heath WR. 83.  2010. The CD8+ dendritic cell subset. Immunol. Rev. 234:118–31 [Google Scholar]
  84. Henri S, Vremec D, Kamath A, Waithman J, Williams S. 84.  et al. 2001. The dendritic cell populations of mouse lymph nodes. J. Immunol. 167:2741–48 [Google Scholar]
  85. Piva L, Tetlak P, Claser C, Karjalainen K, Renia L, Ruedl C. 85.  2012. Cutting edge: Clec9A+ dendritic cells mediate the development of experimental cerebral malaria. J. Immunol. 189:31128–32 [Google Scholar]
  86. Granja AG, Leal E, Pignatelli J, Castro R, Abós B. 86.  et al. 2015. Identification of teleost skin CD8α+ dendritic-like cells, representing a potential common ancestor for mammalian cross-presenting dendritic cells. J. Immunol. 195:41825–37 [Google Scholar]
  87. Contreras V, Urien C, Guiton R, Alexandre Y, Vu Manh T-P. 87.  et al. 2010. Existence of CD8α-like dendritic cells with a conserved functional specialization and a common molecular signature in distant mammalian species. J. Immunol. 185:63313–25 [Google Scholar]
  88. Jardine L, Barge D, Ames-Draycott A, Pagan S, Cookson S. 88.  et al. 2013. Rapid detection of dendritic cell and monocyte disorders using CD4 as a lineage marker of the human peripheral blood antigen-presenting cell compartment. Front. Immunol. 4:495 [Google Scholar]
  89. Schlitzer A, McGovern N, Teo P, Zelante T, Atarashi K. 89.  et al. 2013. IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses. Immunity 38:5970–83 [Google Scholar]
  90. Bajaña S, Roach K, Turner S, Paul J, Kovats S. 90.  2012. IRF4 promotes cutaneous dendritic cell migration to lymph nodes during homeostasis and inflammation. J. Immunol. 189:73368–77 [Google Scholar]
  91. Tailor P, Tamura T, Morse HC III, Ozato K. 91.  2008. The BXH2 mutation in IRF8 differentially impairs dendritic cell subset development in the mouse. Blood 111:1942–45 [Google Scholar]
  92. Haniffa M, Ginhoux F, Wang X-N, Bigley V, Abel M. 92.  et al. 2009. Differential rates of replacement of human dermal dendritic cells and macrophages during hematopoietic stem cell transplantation. J. Exp. Med. 206:2371–85 [Google Scholar]
  93. Kumamoto Y, Linehan M, Weinstein JS, Laidlaw BJ, Craft JE, Iwasaki A. 93.  2013. CD301b+ dermal dendritic cells drive T helper 2 cell-mediated immunity. Immunity 39:4733–43 [Google Scholar]
  94. Gao Y, Nish SA, Jiang R, Hou L, Licona-Limón P. 94.  et al. 2013. Control of T helper 2 responses by transcription factor IRF4-dependent dendritic cells. Immunity 17:722–32 [Google Scholar]
  95. Ochiai S, Roediger B, Abtin A, Shklovskaya E, Fazekas de St Groth B. 95.  et al. 2014. CD326loCD103loCD11blo dermal dendritic cells are activated by thymic stromal lymphopoietin during contact sensitization in mice. J. Immunol. 193:52504–11 [Google Scholar]
  96. Tussiwand R, Everts B, Grajales-Reyes GE, Kretzer NM, Iwata A. 96.  et al. 2015. Klf4 expression in conventional dendritic cells is required for T helper 2 cell responses. Immunity 42:5916–28 [Google Scholar]
  97. Bedoui S, Heath WR. 97.  2015. Krüppel-ling of IRF4-dependent DCs into two functionally distinct DC subsets. Immunity 42:5785–87 [Google Scholar]
  98. Lehtonen A, Veckman V, Nikula T, Lahesmaa R, Kinnunen L. 98.  et al. 2005. Differential expression of IFN regulatory factor 4 gene in human monocyte-derived dendritic cells and macrophages. J. Immunol. 175:106570–79 [Google Scholar]
  99. McGovern N, Schlitzer A, Gunawan M, Jardine L, Shin A. 99.  et al. 2014. Human dermal CD14+ cells are a transient population of monocyte-derived macrophages. Immunity 41:3465–77 [Google Scholar]
  100. Bigley V, Haniffa M, Doulatov S, Wang X-N, Dickinson R. 100.  et al. 2011. The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency. J. Exp. Med. 208:2227–34 [Google Scholar]
  101. Ginhoux F, Guilliams M. 101.  2016. Tissue-resident macrophage ontogeny and homeostasis. Immunity 44:3439–49 [Google Scholar]
  102. Lavin Y, Winter D, Blecher-Gonen R, David E, Keren-Shaul H. 102.  et al. 2014. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 159:61312–26 [Google Scholar]
  103. Tamoutounour S, Guilliams M, Montanana Sanchis F, Liu H, Terhorst D. 103.  et al. 2013. Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin. Immunity 39:5925–38 [Google Scholar]
  104. Gosselin D, Link VM, Romanoski CE, Fonseca GJ, Eichenfield DZ. 104.  et al. 2014. Environment drives selection and function of enhancers controlling tissue-specific macrophage identities. Cell 159:61327–40 [Google Scholar]
  105. Satpathy AT, Wumesh KC, Albring JC, Edelson BT, Kretzer NM. 105.  et al. 2012. Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages. J. Exp. Med. 209:61135–52 [Google Scholar]
  106. Meredith MM, Liu K, Darasse-Jeze G, Kamphorst AO, Schreiber HA. 106.  et al. 2012. Expression of the zinc finger transcription factor zDC (Zbtb46, Btbd4) defines the classical dendritic cell lineage. J. Exp. Med. 209:61153–65 [Google Scholar]
  107. Serbina NV, Salazar-Mather TP, Biron CA, Kuziel WA, Pamer EG. 107.  2003. TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection. Immunity 19:159–70 [Google Scholar]
  108. Lowes MA, Chamian F, Abello MV, Fuentes-Duculan J, Lin S-L. 108.  et al. 2005. Increase in TNF-α and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a). PNAS 102:5219057–62 [Google Scholar]
  109. Wollenberg A, Kraft S, Hanau D, Bieber T. 109.  1996. Immunomorphological and ultrastructural characterization of Langerhans cells and a novel, inflammatory dendritic epidermal cell (IDEC) population in lesional skin of atopic eczema. J. Investig. Dermatol. 106:3446–53 [Google Scholar]
  110. Hänsel A, Günther C, Ingwersen J, Starke J, Schmitz M. 110.  et al. 2011. Human slan (6-sulfo LacNAc) dendritic cells are inflammatory dermal dendritic cells in psoriasis and drive strong TH17/TH1 T-cell responses. J. Allergy Clin. Immunol. 127:3787–94.e-9 [Google Scholar]
  111. Reizis B, Bunin A, Ghosh HS, Lewis KL, Sisirak V. 111.  2011. Plasmacytoid dendritic cells: recent progress and open questions. Annu. Rev. Immunol. 29:163–83 [Google Scholar]
  112. Grouard G, Rissoan MC, Filgueira L, Durand I, Banchereau J, Liu YJ. 112.  1997. The enigmatic plasmacytoid T cells develop into dendritic cells with interleukin (IL)-3 and CD40-ligand. J. Exp. Med. 185:61101–11 [Google Scholar]
  113. Matsui T, Connolly JE, Michnevitz M, Chaussabel D, Yu CI. 113.  et al. 2009. CD2 distinguishes two subsets of human plasmacytoid dendritic cells with distinct phenotype and functions. J. Immunol. 182:116815–23 [Google Scholar]
  114. Bar-On L, Birnberg T, Lewis KL, Bruder D, Hildner K. 114.  CX3CR1+ CD8α+ dendritic cells are a steady-state population related to plasmacytoid dendritic cells. PNAS 107:14745–50 [Google Scholar]
  115. Swiecki M, Colonna M. 115.  2015. The multifaceted biology of plasmacytoid dendritic cells. Nat. Rev. Immunol. 15:8471–85 [Google Scholar]
  116. Cella M, Jarrossay D, Facchetti F, Alebardi O, Nakajima H. 116.  et al. 1999. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat. Med. 5:8919–23 [Google Scholar]
  117. McNiff JM, Kaplan DH. 117.  2008. Plasmacytoid dendritic cells are present in cutaneous dermatomyositis lesions in a pattern distinct from lupus erythematosus. J. Cutan. Pathol. 35:5452–56 [Google Scholar]
  118. Nestle FO, Conrad C, Tun-Kyi A, Homey B, Gombert M. 118.  et al. 2005. Plasmacytoid predendritic cells initiate psoriasis through interferon-α production. J. Exp. Med. 202:1135–43 [Google Scholar]
  119. Siegal FP, Kadowaki N, Shodell M, Fitzgerald-Bocarsly PA, Shah K. 119.  et al. 1999. The nature of the principal type 1 interferon-producing cells in human blood. Science 284:54211835–37 [Google Scholar]
  120. Banchereau J, Steinman RM. 120.  1998. Dendritic cells and the control of immunity. Nature 392:6673245–52 [Google Scholar]
  121. Steinman RM, Hawiger D, Nussenzweig MC. 121.  2003. Tolerogenic dendritic cells. Annu. Rev. Immunol. 21:685–711 [Google Scholar]
  122. Bar-On L, Jung S. 122.  2010. Defining dendritic cells by conditional and constitutive cell ablation. Immunol. Rev. 234:176–89 [Google Scholar]
  123. Dickinson RE, Milne P, Jardine L, Zandi S, Swierczek SI. 123.  et al. 2014. The evolution of cellular deficiency in GATA2 mutation. Blood 123:6863–74 [Google Scholar]
  124. Hawiger D, Inaba K, Dorsett Y, Guo M, Mahnke K. 124.  et al. 2001. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J. Exp. Med. 194:6769–79 [Google Scholar]
  125. Bonifaz L, Bonnyay D, Mahnke K, Rivera M, Nussenzweig MC, Steinman RM. 125.  2002. Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J. Exp. Med. 196:121627–38 [Google Scholar]
  126. Joffre OP, Sancho D, Zelenay S, Keller AM, Reis e Sousa C. 126.  2010. Efficient and versatile manipulation of the peripheral CD4+ T-cell compartment by antigen targeting to DNGR-1/CLEC9A. Eur. J. Immunol. 40:51255–65 [Google Scholar]
  127. Anandasabapathy N, Feder R, Mollah S, Tse S-W, Longhi MP. 127.  et al. 2014. Classical Flt3L-dependent dendritic cells control immunity to protein vaccine. J. Exp. Med. 211:91875–91 [Google Scholar]
  128. Jiang A, Bloom O, Ono S, Cui W, Unternaehrer J. 128.  et al. 2007. Disruption of E-cadherin-mediated adhesion induces a functionally distinct pathway of dendritic cell maturation. Immunity 27:4610–24 [Google Scholar]
  129. Manicassamy S, Reizis B, Ravindran R, Nakaya H, Salazar-Gonzalez RM. 129.  et al. 2010. Activation of β-catenin in dendritic cells regulates immunity versus tolerance in the intestine. Science 329:5993849–53 [Google Scholar]
  130. Baratin M, Foray C, Demaria O, Habbeddine M, Pollet E. 130.  et al. 2015. Homeostatic NF-κB signaling in steady-state migratory dendritic cells regulates immune homeostasis and tolerance. Immunity 42:4627–39 [Google Scholar]
  131. Zhou L, Lopes JE, Chong MMW, Ivanov II, Min R. 131.  et al. 2008. TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function. Nature 453:7192236–40 [Google Scholar]
  132. Marie JC, Letterio JJ, Gavin M, Rudensky AY. 132.  2005. TGF-β1 maintains suppressor function and Foxp3 expression in CD4+CD25 + regulatory T cells. J. Exp. Med. 201:71061–67 [Google Scholar]
  133. Hill JA, Hall JA, Sun C-M, Cai Q, Ghyselinck N. 133.  et al. 2008. Retinoic acid enhances Foxp3 induction indirectly by relieving inhibition from CD4+CD44hi cells. Immunity 29:5758–70 [Google Scholar]
  134. Idoyaga J, Fiorese C, Zbytnuik L, Lubkin A, Miller J. 134.  et al. 2013. Specialized role of migratory dendritic cells in peripheral tolerance induction. J. Clin. Investig. 123:844–54 [Google Scholar]
  135. Yao C, Zurawski SM, Jarrett ES, Chicoine B, Crabtree J. 135.  et al. 2015. Skin dendritic cells induce follicular helper T cells and protective humoral immune responses. J. Allergy Clin. Immunol. 136:1387–97.e7 [Google Scholar]
  136. Li J, Ahmet F, Sullivan LC, Brooks AG, Kent SJ. 136.  et al. 2015. Antibodies targeting Clec9A promote strong humoral immunity without adjuvant in mice and non-human primates. Eur. J. Immunol. 45:3854–64 [Google Scholar]
  137. Seneschal J, Clark RA, Gehad A, Baecher-Allan CM, Kupper TS. 137.  2012. Human epidermal Langerhans cells maintain immune homeostasis in skin by activating skin resident regulatory T cells. Immunity 36:5873–84 [Google Scholar]
  138. Liu Z, Gerner MY, van Panhuys N, Levine AG, Rudensky AY, Germain RN. 138.  2015. Immune homeostasis enforced by co-localized effector and regulatory T cells. Nature 528:7581225–30 [Google Scholar]
  139. Guilliams M, Crozat K, Henri S, Tamoutounour S, Grenot P. 139.  et al. 2010. Skin-draining lymph nodes contain dermis-derived CD103 dendritic cells that constitutively produce retinoic acid and induce Foxp3+ regulatory T cells. Blood 115:101958–68 [Google Scholar]
  140. Li D, Romain G, Flamar A-L, Duluc D, Dullaers M. 140.  et al. 2012. Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generates IL-10-producing suppressive CD4+ T cells. J. Exp. Med. 209:1109–21 [Google Scholar]
  141. Jongbloed SL, Kassianos AJ, McDonald KJ, Clark GJ, Ju X. 141.  et al. 2010. Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens. J. Exp. Med. 207:61247–60 [Google Scholar]
  142. Joffre OP, Segura E, Savina A, Amigorena S. 142.  2012. Cross-presentation by dendritic cells. Nat. Rev. Immunol. 12:8557–69 [Google Scholar]
  143. Igyarto BZ, Haley K, Ortner D, Bobr A, Gerami-Nejad M. 143.  et al. 2011. Skin-resident murine dendritic cell subsets promote distinct and opposing antigen-specific T helper cell responses. Immunity 35:2260–72 [Google Scholar]
  144. Naik S, Bouladoux N, Linehan JL, Han S-J, Harrison OJ. 144.  et al. 2015. Commensal-dendritic-cell interaction specifies a unique protective skin immune signature. Nature 520:7545104–8 [Google Scholar]
  145. Bedoui S, Whitney PG, Waithman J, Eidsmo L, Wakim L. 145.  et al. 2009. Cross-presentation of viral and self antigens by skin-derived CD103+ dendritic cells. Nat. Immunol. 10:5488–95 [Google Scholar]
  146. Hor JL, Whitney PG, Zaid A, Brooks AG, Heath WR, Mueller SN. 146.  2015. Spatiotemporally distinct interactions with dendritic cell subsets facilitates CD4+ and CD8+ T cell activation to localized viral infection. Immunity 43:554–65 [Google Scholar]
  147. Eickhoff S, Brewitz A, Gerner MY, Klauschen F, Komander K. 147.  et al. 2015. Robust anti-viral immunity requires multiple distinct T cell-dendritic cell interactions. Cell 162:61322–37 [Google Scholar]
  148. Kitano M, Yamazaki C, Takumi A, Ikeno T, Hemmi H. 148.  et al. 2016. Imaging of the cross-presenting dendritic cell subsets in the skin-draining lymph node. PNAS 113:41044–49 [Google Scholar]
  149. Goel N, Lee HK, Docherty JJ, Zamora M, Linehan MM. 149.  et al. 2002. A modification of the epidermal scarification model of herpes simplex virus infection to achieve a reproducible and uniform progression of disease. J. Virol. Methods 106:2153–58 [Google Scholar]
  150. Flacher V, Tripp CH, Mairhofer DG, Steinman RM, Stoitzner P. 150.  et al. 2014. Murine Langerin+ dermal dendritic cells prime CD8+ T cells while Langerhans cells induce cross-tolerance. EMBO Mol. Med. 6:91191–204 [Google Scholar]
  151. Chu C-C, Ali N, Karagiannis P, Di Meglio P, Skowera A. 151.  et al. 2012. Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation. J. Exp. Med. 209:5935–45 [Google Scholar]
  152. Artyomov MN, Munk A, Gorvel L, Korenfeld D, Cella M. 152.  et al. 2015. Modular expression analysis reveals functional conservation between human Langerhans cells and mouse cross-priming dendritic cells. J. Exp. Med. 212:5743–57 [Google Scholar]
  153. Mashayekhi M, Sandau MM, Dunay IR, Frickel EM, Khan A. 153.  et al. 2011. CD8α+ dendritic cells are the critical source of interleukin-12 that controls acute infection by Toxoplasma gondii tachyzoites. Immunity 35:2249–59 [Google Scholar]
  154. Martínez-López M, Iborra S, Conde-Garrosa R, Sancho D. 154.  2015. Batf3-dependent CD103+ dendritic cells are major producers of IL-12 that drive local Th1 immunity against Leishmania major infection in mice. Eur. J. Immunol. 45:1119–29 [Google Scholar]
  155. Kashem SW, Igyarto BZ, Gerami-Nejad M, Kumamoto Y, Mohammed J. 155.  et al. 2015. Candida albicans morphology and dendritic cell subsets determine T helper cell differentiation. Immunity 42:2356–66 [Google Scholar]
  156. Zhao X, Deak E, Soderberg K, Linehan M, Spezzano D. 156.  et al. 2003. Vaginal submucosal dendritic cells, but not Langerhans cells, induce protective Th1 responses to herpes simplex virus-2. J. Exp. Med. 197:2153–62 [Google Scholar]
  157. Bollampalli VP, Harumi Yamashiro L, Feng X, Bierschenk D, Gao Y. 157.  et al. 2015. BCG skin infection triggers IL-1R-MyD88-dependent migration of EpCAMlow CD11bhigh skin dendritic cells to draining lymph node during CD4+ T-cell priming. PLOS Pathog 11:10e1005206 [Google Scholar]
  158. León B, López-Bravo M, Ardavín C. 158.  2007. Monocyte-derived dendritic cells formed at the infection site control the induction of protective T helper 1 responses against Leishmania. . Immunity 26:4519–31 [Google Scholar]
  159. Zhan Y, Xu Y, Seah S, Brady JL, Carrington EM. 159.  et al. 2010. Resident and monocyte-derived dendritic cells become dominant IL-12 producers under different conditions and signaling pathways. J. Immunol. 185:42125–33 [Google Scholar]
  160. Kumamoto Y, Denda-Nagai K, Aida S, Higashi N, Irimura T. 160.  2009. MGL2 dermal dendritic cells are sufficient to initiate contact hypersensitivity in vivo. PLOS ONE 4:5e5619 [Google Scholar]
  161. Kitajima M, Ziegler SF. 161.  2013. Cutting edge: Identification of the thymic stromal lymphopoietin-responsive dendritic cell subset critical for initiation of type 2 contact hypersensitivity. J. Immunol. 191:104903–7 [Google Scholar]
  162. Bell BD, Kitajima M, Larson RP, Stoklasek TA, Dang K. 162.  et al. 2013. The transcription factor STAT5 is critical in dendritic cells for the development of TH2 but not TH1 responses. Nat. Immunol. 14:4364–71 [Google Scholar]
  163. 163.  Deleted in proof
  164. Everts B, Tussiwand R, Dreesen L, Fairfax KC, Huang SC-C. 164.  et al. 2016. Migratory CD103+ dendritic cells suppress helminth-driven type 2 immunity through constitutive expression of IL-12. J. Exp. Med. 213:135–51 [Google Scholar]
  165. Halim TYF, Hwang YY, Scanlon ST, Zaghouani H, Garbi N. 165.  et al. 2016. Group 2 innate lymphoid cells license dendritic cells to potentiate memory TH2 cell responses. Nat. Immunol. 17:157–64 [Google Scholar]
  166. Korn T, Bettelli E, Oukka M, Kuchroo VK. 166.  2009. IL-17 and Th17 cells. Annu. Rev. Immunol. 27:485–517 [Google Scholar]
  167. Hernández-Santos N, Gaffen SL. 167.  2012. Th17 cells in immunity to Candida albicans. . Cell Host Microbe 11:5425–35 [Google Scholar]
  168. Randall KL, Chan SS-Y, Ma CS, Fung I, Mei Y. 168.  et al. 2011. DOCK8 deficiency impairs CD8 T cell survival and function in humans and mice. J. Exp. Med. 208:112305–20 [Google Scholar]
  169. Harada Y, Tanaka Y, Terasawa M, Pieczyk M, Habiro K. 169.  et al. 2012. DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migration during immune responses. Blood 119:194451–61 [Google Scholar]
  170. Haley K, Igyarto BZ, Ortner D, Bobr A, Kashem S. 170.  et al. 2012. Langerhans cells require MyD88-dependent signals for Candida albicans response but not for contact hypersensitivity or migration. J. Immunol. 188:94334–39 [Google Scholar]
  171. Kobayashi T, Glatz M, Horiuchi K, Kawasaki H, Akiyama H. 171.  et al. 2015. Dysbiosis and Staphylococcus aureus colonization drives inflammation in atopic dermatitis. Immunity 42:4756–66 [Google Scholar]
  172. Mathers AR, Janelsins BM, Rubin JP, Tkacheva OA, Shufesky WJ. 172.  et al. 2009. Differential capability of human cutaneous dendritic cell subsets to initiate Th17 responses. J. Immunol. 182:2921–33 [Google Scholar]
  173. Linehan JL, Dileepan T, Kashem SW, Kaplan DH, Cleary P, Jenkins MK. 173.  2015. Generation of Th17 cells in response to intranasal infection requires TGF-β1 from dendritic cells and IL-6 from CD301b+ dendritic cells. PNAS 112:4112782–87 [Google Scholar]
  174. Nakajima S, Igyarto BZ, Honda T, Egawa G, Otsuka A. 174.  et al. 2012. Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling. J. Allergy Clin. Immunol. 129:41048–55.e6 [Google Scholar]
  175. Zimara N, Florian C, Schmid M, Malissen B, Kissenpfennig A. 175.  et al. 2014. Langerhans cells promote early germinal center formation in response to Leishmania-derived cutaneous antigens. Eur. J. Immunol. 44:102955–67 [Google Scholar]
  176. Kumamoto Y, Linehan M, Weinstein JS, Laidlaw BJ, Craft JE, Iwasaki A. 176.  2013. CD301b+ dermal dendritic cells drive T helper 2 cell-mediated immunity. Immunity 39:4733–43 [Google Scholar]
  177. Kumamoto Y, Hirai T, Wong PW, Kaplan DH, Iwasaki A. 177.  2016. CD301b+ dendritic cells suppress T follicular helper cells and antibody responses to protein antigens. eLife 2016:17979 [Google Scholar]
  178. Lahoud MH, Ahmet F, Kitsoulis S, Wan SS, Vremec D. 178.  et al. 2011. Targeting antigen to mouse dendritic cells via Clec9A induces potent CD4 T cell responses biased toward a follicular helper phenotype. J. Immunol. 187:2842–50 [Google Scholar]
  179. Park HY, Light A, Lahoud MH, Caminschi I, Tarlinton DM, Shortman K. 179.  2013. Evolution of B cell responses to Clec9A-targeted antigen. J. Immunol. 191:104919–25 [Google Scholar]
  180. Clark RA, Chong B, Mirchandani N, Brinster NK, Yamanaka K. 180.  et al. 2006. The vast majority of CLA+ T cells are resident in normal skin. J. Immunol. 176:74431–39 [Google Scholar]
  181. Natsuaki Y, Egawa G, Nakamizo S, Ono S, Hanakawa S. 181.  et al. 2014. Perivascular leukocyte clusters are essential for efficient activation of effector T cells in the skin. Nat. Immunol. 15:111064–69 [Google Scholar]
  182. Iijima N, Iwasaki A. 182.  2014. T cell memory: a local macrophage chemokine network sustains protective tissue-resident memory CD4 T cells. Science 346:620593–98 [Google Scholar]
  183. Collins N, Jiang X, Zaid A, Macleod BL, Li J. 183.  et al. 2016. Skin CD4+ memory T cells exhibit combined cluster-mediated retention and equilibration with the circulation. Nat. Commun. 7:11514 [Google Scholar]
  184. Kim T-G, Jee H, Fuentes-Duculan J, Wu WH, Byamba D. 184.  et al. 2014. Dermal clusters of mature dendritic cells and T cells are associated with the CCL20/CCR6 chemokine system in chronic psoriasis. J. Investig. Dermatol. 134:51462–65 [Google Scholar]
  185. Zaid A, Mackay LK, Rahimpour A, Braun A, Veldhoen M. 185.  et al. 2014. Persistence of skin-resident memory T cells within an epidermal niche. PNAS 111:145307–12 [Google Scholar]
  186. Wakim LM, Waithman J, van Rooijen N, Heath WR, Carbone FR. 186.  2008. Dendritic cell-induced memory T cell activation in nonlymphoid tissues. Science 319:5860198–202 [Google Scholar]
  187. McLachlan JB, Catron DM, Moon JJ, Jenkins MK. 187.  2009. Dendritic cell antigen presentation drives simultaneous cytokine production by effector and regulatory T cells in inflamed skin. Immunity 30:2277–88 [Google Scholar]
  188. Girard-Madoux MJH, Kel JM, Reizis B, Clausen BE. 188.  2012. IL-10 controls dendritic cell-induced T-cell reactivation in the skin to limit contact hypersensitivity. J. Allergy Clin. Immunol. 129:1143–50.e10 [Google Scholar]
  189. Brigl M, Brenner MB. 189.  2004. CD1: antigen presentation and T cell function. Annu. Rev. Immunol. 22:1817–90 [Google Scholar]
  190. de Jong A, Cheng T-Y, Huang S, Gras S, Birkinshaw RW. 190.  et al. 2014. CD1a-autoreactive T cells recognize natural skin oils that function as headless antigens. Nat. Immunol. 15:2177–85 [Google Scholar]
  191. Hunger RE, Sieling PA, Ochoa MT, Sugaya M, Burdick AE. 191.  et al. 2004. Langerhans cells utilize CD1a and langerin to efficiently present nonpeptide antigens to T cells. J. Clin. Investig. 113:5701–8 [Google Scholar]
  192. Bourgeois EA, Subramaniam S, Cheng T-Y, de Jong A, Layre E. 192.  et al. 2015. Bee venom processes human skin lipids for presentation by CD1a. J. Exp. Med. 212:2149–63 [Google Scholar]
  193. Jarrett R, Salio M, Lloyd-Lavery A, Subramaniam S, Bourgeois E. 193.  et al. 2016. Filaggrin inhibits generation of CD1a neolipid antigens by house dust mite-derived phospholipase. Sci. Transl. Med. 8:325325ra18 [Google Scholar]
  194. Kim JH, Hu Y, Yongqing T, Kim J, Hughes VA. 194.  et al. 2016. CD1a on Langerhans cells controls inflammatory skin disease. Nat. Immunol. 17:1159–66 [Google Scholar]
  195. Cerny D, Thi Le DH, The TD, Zuest R, Kg S. 195.  et al. 2016. Complete human CD1a deficiency on Langerhans cells due to a rare point mutation in the coding sequence. J. Allergy Clin. Immunol. 138:61709–12.e11 [Google Scholar]
  196. Gray EE, Ramírez-Valle F, Xu Y, Wu S, Wu Z. 196.  et al. 2013. Deficiency in IL-17-committed Vγ4+ γδ T cells in a spontaneous Sox13-mutant CD45.1+ congenic mouse substrain provides protection from dermatitis. Nat. Immunol. 14:6584–92 [Google Scholar]
  197. Sumaria N, Roediger B, Ng LG, Qin J, Pinto R. 197.  et al. 2011. Cutaneous immunosurveillance by self-renewing dermal γδ T cells. J. Exp. Med. 208:3505–18 [Google Scholar]
  198. Cho JS, Pietras EM, Garcia NC, Ramos RI, Farzam DM. 198.  et al. 2010. IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice. J. Clin. Investig. 120:51762–73 [Google Scholar]
  199. Kashem SW, Riedl MS, Yao C, Honda CN, Vulchanova L, Kaplan DH. 199.  2015. Nociceptive sensory fibers drive interleukin-23 production from CD301b+ dermal dendritic cells and drive protective cutaneous immunity. 433515–26
  200. Riol-Blanco L, Ordovas-Montanes J, Perro M, Naval E, Thiriot A. 200.  et al. 2014. Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation. Nature 510:7503157–61 [Google Scholar]
  201. Kashem SW, Riedl MS, Yao C, Honda CN, Vulchanova L, Kaplan DH. 201.  2015. Nociceptive sensory fibers drive interleukin-23 production from CD301b+ dermal dendritic cells and drive protective cutaneous immunity. Immunity 43:3515–26 [Google Scholar]
  202. Yoshiki R, Kabashima K, Honda T, Nakamizo S, Sawada Y. 202.  et al. 2014. IL-23 from Langerhans cells is required for the development of imiquimod-induced psoriasis-like dermatitis by induction of IL-17A-producing γδ T cells. J. Investig. Dermatol. 134:71912–21 [Google Scholar]
  203. Wohn C, Ober-Blöbaum JL, Haak S, Pantelyushin S, Cheong C. 203.  et al. 2013. Langerinneg conventional dendritic cells produce IL-23 to drive psoriatic plaque formation in mice. PNAS 110:2610723–28 [Google Scholar]
  204. Gaspari AA, Katz SI. 204.  1988. Induction and functional characterization of class II MHC (Ia) antigens on murine keratinocytes. J. Immunol. 140:92956–63 [Google Scholar]
  205. Fan D, Coughlin LA, Neubauer MM, Kim J, Kim MS. 205.  et al. 2015. Activation of HIF-1α and LL-37 by commensal bacteria inhibits Candida albicans colonization. Nat. Med. 21:7808–14 [Google Scholar]
  206. Griffiths CE, Nickoloff BJ. 206.  1989. Keratinocyte intercellular adhesion molecule-1 (ICAM-1) expression precedes dermal T lymphocytic infiltration in allergic contact dermatitis (Rhus dermatitis). Am. J. Pathol. 135:61045–53 [Google Scholar]
  207. Kel JM, Girard-Madoux MJH, Reizis B, Clausen BE. 207.  2010. TGF-beta is required to maintain the pool of immature Langerhans cells in the epidermis. J. Immunol. 185:63248–55 [Google Scholar]
  208. Bobr A, Igyarto BZ, Haley KM, Li MO, Flavell RA, Kaplan DH. 208.  2012. Autocrine/paracrine TGF-β1 inhibits Langerhans cell migration. PNAS 109:2610492–97 [Google Scholar]
  209. Modi BG, Neustadter J, Binda E, Lewis J, Filler RB. 209.  et al. 2012. Langerhans cells facilitate epithelial DNA damage and squamous cell carcinoma. Science 335:6064104–8 [Google Scholar]
  210. Lewis JM, Bürgler CD, Fraser JA, Liao H, Golubets K. 210.  et al. 2015. Mechanisms of chemical cooperative carcinogenesis by epidermal Langerhans cells. J. Investig. Dermatol. 135:51405–14 [Google Scholar]
  211. Lewis JM, Bürgler CD, Freudzon M, Golubets K, Gibson JF. 211.  et al. 2015. Langerhans cells facilitate UVB-induced epidermal carcinogenesis. J. Investig. Dermatol. 135:112824–33 [Google Scholar]
  212. Fuertes MB, Kacha AK, Kline J, Woo S-R, Kranz DM. 212.  et al. 2011. Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8α+ dendritic cells. J. Exp. Med. 208:102005–16 [Google Scholar]
  213. Broz ML, Binnewies M, Boldajipour B, Nelson AE, Pollack JL. 213.  et al. 2014. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity. Cancer Cell 26:5638–52 [Google Scholar]
  214. Salmon H, Idoyaga J, Rahman A, Leboeuf M, Remark R. 214.  et al. 2016. Expansion and activation of CD103+ dendritic cell progenitors at the tumor site enhances tumor responses to therapeutic PD-L1 and BRAF inhibition. Immunity 44:4924–38 [Google Scholar]
  215. Wimmers F, Schreibelt G, Sköld AE, Figdor CG, De Vries IJM. 215.  2014. Paradigm shift in dendritic cell-based immunotherapy: from in vitro generated monocyte-derived DCs to naturally circulating DC subsets. Front. Immunol. 5:Suppl. 8165 [Google Scholar]
  216. Martincorena I, Campbell PJ. 216.  2015. Somatic mutation in cancer and normal cells. Science 349:62551483–89 [Google Scholar]
  217. Martincorena I, Roshan A, Gerstung M, Ellis P, Van Loo P. 217.  et al. 2015. Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin. Science 348:6237880–86 [Google Scholar]
  218. Colegio OR, Chu N-Q, Szabo AL, Chu T, Rhebergen AM. 218.  et al. 2014. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature 513:7519559–63 [Google Scholar]
  219. Spranger S, Bao R, Gajewski TF. 219.  2015. Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature 523:7559231–35 [Google Scholar]
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