1932

Abstract

Inflammation is an unstable state. It either resolves or persists. Why inflammation persists and the factors that define tissue tropism remain obscure. Increasing evidence suggests that tissue-resident stromal cells not only provide positional memory but also actively regulate the differential accumulation of inflammatory cells within inflamed tissues. Furthermore, at many sites of chronic inflammation, structures that mimic secondary lymphoid tissues are observed, suggesting that chronic inflammation and lymphoid tissue formation share common activation programs. Similarly, blood and lymphatic endothelial cells contribute to tissue homeostasis and disease persistence in chronic inflammation. This review highlights our increasing understanding of the role of stromal cells in inflammation and summarizes the novel immunological role that stromal cells exert in the persistence of inflammatory diseases.

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2015-03-21
2024-04-21
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Literature Cited

  1. Kuby J. 1.  1997. Immunology New York: W.H. Freeman, 3rd ed..
  2. Austyn JM, Wood KJ. 2.  1993. Principles of Cellular and Molecular Immunology Oxford, UK: Oxford Univ. Press
  3. Prati C, Demougeot C, Guillot X, Godfrin-Valnet M, Wendling D. 3.  2014. Endothelial dysfunction in joint disease. Joint Bone Spine 81:386–91 [Google Scholar]
  4. Parsonage G, Filer AD, Haworth O, Nash GB, Rainger GE. 4.  et al. 2005. A stromal address code defined by fibroblasts. Trends Immunol. 26:150–56 [Google Scholar]
  5. Filer A, Raza K, Salmon M, Buckley CD. 5.  2008. The role of chemokines in leucocyte-stromal interactions in rheumatoid arthritis. Front. Biosci. 13:2674–85 [Google Scholar]
  6. Flavell SJ, Hou TZ, Lax S, Filer AD, Salmon M. 6.  et al. 2008. Fibroblasts as novel therapeutic targets in chronic inflammation. Br. J. Pharmacol. 153:Suppl. 1S241–46 [Google Scholar]
  7. Greenbaum A, Hsu YM, Day RB, Schuettpelz LG, Christopher MJ. 7.  et al. 2013. CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature 495:227–30 [Google Scholar]
  8. Aloisi F, Pujol-Borrell R. 8.  2006. Lymphoid neogenesis in chronic inflammatory diseases. Nat. Rev. Immunol. 6:205–17 [Google Scholar]
  9. Klareskog L, Catrina AI, Paget S. 9.  2009. Rheumatoid arthritis. Lancet 373:659–72 [Google Scholar]
  10. Bhowmick NA, Neilson EG, Moses HL. 10.  2004. Stromal fibroblasts in cancer initiation and progression. Nature 432:332–37 [Google Scholar]
  11. Chang HY, Chi JT, Dudoit S, Bondre C, van de Rijn M. 11.  et al. 2002. Diversity, topographic differentiation, and positional memory in human fibroblasts. PNAS 99:12877–82 [Google Scholar]
  12. Chang SK, Gu Z, Brenner MB. 12.  2010. Fibroblast-like synoviocytes in inflammatory arthritis pathology: the emerging role of cadherin-11. Immunol. Rev. 233:256–66 [Google Scholar]
  13. Mor A, Abramson SB, Pillinger MH. 13.  2005. The fibroblast-like synovial cell in rheumatoid arthritis: a key player in inflammation and joint destruction. Clin. Immunol. 115:118–28 [Google Scholar]
  14. Buckley CD. 14.  2003. Why do leucocytes accumulate within chronically inflamed joints?. Rheumatology 42:1433–44 [Google Scholar]
  15. Firestein GS. 15.  1996. Invasive fibroblast-like synoviocytes in rheumatoid arthritis: passive responders or transformed aggressors?. Arthritis Rheum. 39:1781–90 [Google Scholar]
  16. Lee DM, Kiener HP, Agarwal SK, Noss EH, Watts GF. 16.  et al. 2007. Cadherin-11 in synovial lining formation and pathology in arthritis. Science 315:1006–10 [Google Scholar]
  17. Kalluri R, Zeisberg M. 17.  2006. Fibroblasts in cancer. Nat. Rev. Cancer 6:392–401 [Google Scholar]
  18. Wilkinson LS, Pitsillides AA, Worrall JG, Edwards JC. 18.  1992. Light microscopic characterization of the fibroblast-like synovial intimal cell (synoviocyte). Arthritis Rheum. 35:1179–84 [Google Scholar]
  19. Zimmermann T, Kunisch E, Pfeiffer R, Hirth A, Stahl HD. 19.  et al. 2001. Isolation and characterization of rheumatoid arthritis synovial fibroblasts from primary culture—primary culture cells markedly differ from fourth-passage cells. Arthritis Res. 3:72–76 [Google Scholar]
  20. Kiener HP, Niederreiter B, Lee DM, Jimenez-Boj E, Smolen JS. 20.  et al. 2009. Cadherin 11 promotes invasive behavior of fibroblast-like synoviocytes. Arthritis Rheum. 60:1305–10 [Google Scholar]
  21. Micke P, Ostman A. 21.  2004. Tumour-stroma interaction: cancer-associated fibroblasts as novel targets in anti-cancer therapy?. Lung Cancer 45:Suppl. 2S163–75 [Google Scholar]
  22. Barsky SH, Green WR, Grotendorst GR, Liotta LA. 22.  1984. Desmoplastic breast carcinoma as a source of human myofibroblasts. Am. J. Pathol. 115:329–33 [Google Scholar]
  23. Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW. 23.  et al. 2007. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449:557–63 [Google Scholar]
  24. Orimo A, Gupta PB, Sgroi DC, Arenzana-Seisdedos F, Delaunay T. 24.  et al. 2005. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121:335–48 [Google Scholar]
  25. Kraman M, Bambrough PJ, Arnold JN, Roberts EW, Magiera L. 25.  et al. 2010. Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-α. Science 330:827–30 [Google Scholar]
  26. Desmoulière A, Darby IA, Gabbiani G. 26.  2003. Normal and pathologic soft tissue remodeling: role of the myofibroblast, with special emphasis on liver and kidney fibrosis. Lab. Investig. 83:1689–707 [Google Scholar]
  27. Ho YY, Lagares D, Tager AM, Kapoor M. 27.  2014. Fibrosis—a lethal component of systemic sclerosis. Nat. Rev. Rheumatol. 10:390–402 [Google Scholar]
  28. Wallach-Dayan SB, Golan-Gerstl R, Breuer R. 28.  2007. Evasion of myofibroblasts from immune surveillance: a mechanism for tissue fibrosis. PNAS 104:20460–65 [Google Scholar]
  29. Filer A, Parsonage G, Smith E, Osborne C, Thomas AM. 29.  et al. 2006. Differential survival of leukocyte subsets mediated by synovial, bone marrow, and skin fibroblasts: site-specific versus activation-dependent survival of T cells and neutrophils. Arthritis Rheum. 54:2096–108 [Google Scholar]
  30. Parsonage G, Falciani F, Burman A, Filer A, Ross E. 30.  et al. 2003. Global gene expression profiles in fibroblasts from synovial, skin and lymphoid tissue reveals distinct cytokine and chemokine expression patterns. Thromb. Haemost. 90:688–97 [Google Scholar]
  31. Bradfield PF, Amft N, Vernon-Wilson E, Exley AE, Parsonage G. 31.  et al. 2003. Rheumatoid fibroblast-like synoviocytes overexpress the chemokine stromal cell-derived factor 1 (CXCL12), which supports distinct patterns and rates of CD4+ and CD8 +T cell migration within synovial tissue. Arthritis Rheum. 48:2472–82 [Google Scholar]
  32. Lally F, Smith E, Filer A, Stone MA, Shaw JS. 32.  et al. 2005. A novel mechanism of neutrophil recruitment in a coculture model of the rheumatoid synovium. Arthritis Rheum. 52:3460–69 [Google Scholar]
  33. McGettrick HM, Smith E, Filer A, Kissane S, Salmon M. 33.  et al. 2009. Fibroblasts from different sites may promote or inhibit recruitment of flowing lymphocytes by endothelial cells. Eur. J. Immunol. 39:113–25 [Google Scholar]
  34. Buckley CD, Filer A, Haworth O, Parsonage G, Salmon M. 34.  2004. Defining a role for fibroblasts in the persistence of chronic inflammatory joint disease. Ann. Rheum. Dis. 63:Suppl. 2ii92–95 [Google Scholar]
  35. Lotz M, Terkeltaub R, Villiger PM. 35.  1992. Cartilage and joint inflammation. Regulation of IL-8 expression by human articular chondrocytes. J. Immunol. 148:466–73 [Google Scholar]
  36. Koch AE, Kunkel SL, Shah MR, Fu R, Mazarakis DD. 36.  et al. 1995. Macrophage inflammatory protein-1β: a C-C chemokine in osteoarthritis. Clin. Immunol. Immunopathol. 77:307–14 [Google Scholar]
  37. Koch AE, Kunkel SL, Burrows JC, Evanoff HL, Haines GK. 37.  et al. 1991. Synovial tissue macrophage as a source of the chemotactic cytokine IL-8. J. Immunol. 147:2187–95 [Google Scholar]
  38. Koch AE, Kunkel SL, Harlow LA, Mazarakis DD, Haines GK. 38.  et al. 1994. Macrophage inflammatory protein-1α: a novel chemotactic cytokine for macrophages in rheumatoid arthritis. J. Clin. Investig. 93:921–28 [Google Scholar]
  39. Nanki T, Shimaoka T, Hayashida K, Taniguchi K, Yonehara S. 39.  et al. 2005. Pathogenic role of the CXCL16-CXCR6 pathway in rheumatoid arthritis. Arthritis Rheum. 52:3004–14 [Google Scholar]
  40. Patel DD, Zachariah JP, Whichard LP. 40.  2001. CXCR3 and CCR5 ligands in rheumatoid arthritis synovium. Clin. Immunol. 98:39–45 [Google Scholar]
  41. Burger JA, Zvaifler NJ, Tsukada N, Firestein GS, Kipps TJ. 41.  2001. Fibroblast-like synoviocytes support B-cell pseudoemperipolesis via a stromal cell-derived factor-1- and CD106 (VCAM-1)-dependent mechanism. J. Clin. Investig. 107:305–15 [Google Scholar]
  42. Chan A, Filer A, Parsonage G, Kollnberger S, Gundle R. 42.  et al. 2008. Mediation of the proinflammatory cytokine response in rheumatoid arthritis and spondylarthritis by interactions between fibroblast-like synoviocytes and natural killer cells. Arthritis Rheum. 58:707–17 [Google Scholar]
  43. Bombardieri M, Kam NW, Brentano F, Choi K, Filer A. 43.  et al. 2011. A BAFF/APRIL-dependent TLR3-stimulated pathway enhances the capacity of rheumatoid synovial fibroblasts to induce AID expression and Ig class-switching in B cells. Ann. Rheum. Dis. 70:1857–65 [Google Scholar]
  44. Bikker A, Kruize AA, Wenting M, Versnel MA, Bijlsma JWJ. 44.  et al. 2012. Increased interleukin (IL)-7Rα expression in salivary glands of patients with primary Sjögren's syndrome is restricted to T cells and correlates with IL-7 expression, lymphocyte numbers and activity. Ann. Rheum. Dis. 71:1027–33 [Google Scholar]
  45. Ramos-Casals M. 45.  2013. The B-lymphocyte stimulator connection in Sjögren's syndrome. Rheumatology 52:223–25 [Google Scholar]
  46. Muller-Ladner U, Gay S. 46.  2002. MMPs and rheumatoid synovial fibroblasts: Siamese twins in joint destruction?. Ann. Rheum. Dis. 61:957–59 [Google Scholar]
  47. Takayanagi H, Iizuka H, Juji T, Nakagawa T, Yamamoto A. 47.  et al. 2000. Involvement of receptor activator of nuclear factor κB ligand/osteoclast differentiation factor in osteoclastogenesis from synoviocytes in rheumatoid arthritis. Arthritis Rheum. 43:259–69 [Google Scholar]
  48. Muller-Ladner U, Kriegsmann J, Franklin BN, Matsumoto S, Geiler T. 48.  et al. 1996. Synovial fibroblasts of patients with rheumatoid arthritis attach to and invade normal human cartilage when engrafted into SCID mice. Am. J. Pathol. 149:1607–15 [Google Scholar]
  49. Tolboom TC, van der Helm-Van Mil AHM, Nelissen RG, Breedveld FC, Toes RE. 49.  et al. 2005. Invasiveness of fibroblast-like synoviocytes is an individual patient characteristic associated with the rate of joint destruction in patients with rheumatoid arthritis. Arthritis Rheum. 52:1999–2002 [Google Scholar]
  50. Lefèvre S, Knedla A, Tennie C, Kampmann A, Wunrau C. 50.  et al. 2009. Synovial fibroblasts spread rheumatoid arthritis to unaffected joints. Nat. Med. 15:1414–20 [Google Scholar]
  51. Shigeyama Y, Pap T, Kunzler P, Simmen BR, Gay RE. 51.  et al. 2000. Expression of osteoclast differentiation factor in rheumatoid arthritis. Arthritis Rheum. 43:2523–30 [Google Scholar]
  52. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F. 52.  et al. 2006. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–17 [Google Scholar]
  53. Haniffa MA, Collin MP, Buckley CD, Dazzi F. 53.  2009. Mesenchymal stem cells: the fibroblasts' new clothes?. Haematologica 94:258–63 [Google Scholar]
  54. Salem HK, Thiemermann C. 54.  2010. Mesenchymal stromal cells: current understanding and clinical status. Stem Cells 28:585–96 [Google Scholar]
  55. Romieu-Mourez R, François M, Boivin MN, Bouchentouf M, Spaner DE. 55.  et al. 2009. Cytokine modulation of TLR expression and activation in mesenchymal stromal cells leads to a proinflammatory phenotype. J. Immunol. 182:7963–73 [Google Scholar]
  56. Gonzalez MA, Gonzalez-Rey E, Rico L, Buscher D, Delgado M. 56.  2009. Treatment of experimental arthritis by inducing immune tolerance with human adipose-derived mesenchymal stem cells. Arthritis Rheum. 60:1006–19 [Google Scholar]
  57. Schurgers E, Kelchtermans H, Mitera T, Geboes L, Matthys P. 57.  2010. Discrepancy between the in vitro and in vivo effects of murine mesenchymal stem cells on T-cell proliferation and collagen-induced arthritis. Arthritis Res. Ther. 12:R31 [Google Scholar]
  58. Buckner JH. 58.  2010. Mechanisms of impaired regulation by CD4+CD25+FOXP3+ regulatory T cells in human autoimmune diseases. Nat. Rev. Immunol. 10:849–59 [Google Scholar]
  59. Huggenberger R, Siddiqui SS, Brander D, Ullmann S, Zimmermann K. 59.  et al. 2011. An important role of lymphatic vessel activation in limiting acute inflammation. Blood 117:4667–78 [Google Scholar]
  60. Ulvmar MH, Werth K, Braun A, Kelay P, Hub E. 60.  et al. 2014. The atypical chemokine receptor CCRL1 shapes functional CCL21 gradients in lymph nodes. Nat. Immunol. 15:623–30 [Google Scholar]
  61. Osada M, Inoue O, Ding G, Shirai T, Ichise H. 61.  et al. 2012. Platelet activation receptor CLEC-2 regulates blood/lymphatic vessel separation by inhibiting proliferation, migration, and tube formation of lymphatic endothelial cells. J. Biol. Chem. 287:22241–52 [Google Scholar]
  62. Watson SP, Lowe K, Finney BA. 62.  2014. Platelets in lymph vessel development and integrity. Adv. Anat. Embryol. Cell Biol. 214:93–105 [Google Scholar]
  63. Liao S, Ruddle NH. 63.  2006. Synchrony of high endothelial venules and lymphatic vessels revealed by immunization. J. Immunol. 177:3369–79 [Google Scholar]
  64. Pham TH, Baluk P, Xu Y, Grigorova I, Bankovich AJ. 64.  et al. 2010. Lymphatic endothelial cell sphingosine kinase activity is required for lymphocyte egress and lymphatic patterning. J. Exp. Med. 207:17–27 [Google Scholar]
  65. Fletcher AL, Malhotra D, Turley SJ. 65.  2011. Lymph node stroma broaden the peripheral tolerance paradigm. Trends Immunol. 32:12–18 [Google Scholar]
  66. Alitalo K. 66.  2011. The lymphatic vasculature in disease. Nat. Med. 17:1371–80 [Google Scholar]
  67. Flister MJ, Wilber A, Hall KL, Iwata C, Miyazono K. 67.  et al. 2010. Inflammation induces lymphangiogenesis through up-regulation of VEGFR-3 mediated by NF-κB and Prox1. Blood 115:418–29 [Google Scholar]
  68. Alitalo K, Tammela T, Petrova TV. 68.  2005. Lymphangiogenesis in development and human disease. Nature 438:946–53 [Google Scholar]
  69. Kunder CA, St. John AL, Abraham SN. 69.  2011. Mast cell modulation of the vascular and lymphatic endothelium. Blood 118:5383–93 [Google Scholar]
  70. Cursiefen C, Chen L, Borges LP, Jackson D, Cao J. 70.  et al. 2004. VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J. Clin. Investig. 113:1040–50 [Google Scholar]
  71. Hamrah P, Chen L, Zhang Q, Dana MR. 71.  2003. Novel expression of vascular endothelial growth factor receptor (VEGFR)-3 and VEGF-C on corneal dendritic cells. Am. J. Pathol. 163:57–68 [Google Scholar]
  72. Mounzer RH, Svendsen OS, Baluk P, Bergman CM, Padera TP. 72.  et al. 2010. Lymphotoxin-alpha contributes to lymphangiogenesis. Blood 116:2173–82 [Google Scholar]
  73. Lee JY, Park C, Cho YP, Lee E, Kim H. 73.  et al. 2010. Podoplanin-expressing cells derived from bone marrow play a crucial role in postnatal lymphatic neovascularization. Circulation 122:1413–25 [Google Scholar]
  74. Kerjaschki D, Huttary N, Raab I, Regele H, Bojarski-Nagy K. 74.  et al. 2006. Lymphatic endothelial progenitor cells contribute to de novo lymphangiogenesis in human renal transplants. Nat. Med. 12:230–34 [Google Scholar]
  75. Maruyama K, Ii M, Cursiefen C, Jackson DG, Keino H. 75.  et al. 2005. Inflammation-induced lymphangiogenesis in the cornea arises from CD11b-positive macrophages. J. Clin. Investig. 115:2363–72 [Google Scholar]
  76. Jamieson T, Cook DN, Nibbs RJ, Rot A, Nixon C. 76.  et al. 2005. The chemokine receptor D6 limits the inflammatory response in vivo. Nat. Immunol. 6:403–11 [Google Scholar]
  77. Podgrabinska S, Kamalu O, Mayer L, Shimaoka M, Snoeck H. 77.  et al. 2009. Inflamed lymphatic endothelium suppresses dendritic cell maturation and function via Mac-1/ICAM-1-dependent mechanism. J. Immunol. 183:1767–79 [Google Scholar]
  78. Baluk P, Tammela T, Ator E, Lyubynska N, Achen MG. 78.  et al. 2005. Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation. J. Clin. Investig. 115:247–57 [Google Scholar]
  79. von der Weid PY, Rehal S, Ferraz JG. 79.  2011. Role of the lymphatic system in the pathogenesis of Crohn's disease. Curr. Opin. Gastroenterol. 27:335–41 [Google Scholar]
  80. Kajiya K, Detmar M. 80.  2006. An important role of lymphatic vessels in the control of UVB-induced edema formation and inflammation. J. Investig. Dermatol. 126:919–21 [Google Scholar]
  81. Wilkinson LS, Edwards JC. 81.  1991. Demonstration of lymphatics in human synovial tissue. Rheumatol. Int. 11:151–55 [Google Scholar]
  82. Thaunat O, Kerjaschki D, Nicoletti A. 82.  2006. Is defective lymphatic drainage a trigger for lymphoid neogenesis?. Trends Immunol. 27:441–45 [Google Scholar]
  83. Burman A, Haworth O, Hardie DL, Amft EN, Siewert C. 83.  et al. 2005. A chemokine-dependent stromal induction mechanism for aberrant lymphocyte accumulation and compromised lymphatic return in rheumatoid arthritis. J. Immunol. 174:1693–700 [Google Scholar]
  84. Kerjaschki D, Regele HM, Moosberger I, Nagy-Bojarski K, Watschinger B. 84.  et al. 2004. Lymphatic neoangiogenesis in human kidney transplants is associated with immunologically active lymphocytic infiltrates. J. Am. Soc. Nephrol. 15:603–12 [Google Scholar]
  85. Karpanen T, Egeblad M, Karkkainen MJ, Kubo H, Yla-Herttuala S. 85.  et al. 2001. Vascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth. Cancer Res. 61:1786–90 [Google Scholar]
  86. Skobe M, Hawighorst T, Jackson DG, Prevo R, Janes L. 86.  et al. 2001. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat. Med. 7:192–98 [Google Scholar]
  87. Beasley NJ, Prevo R, Banerji S, Leek RD, Moore J. 87.  et al. 2002. Intratumoral lymphangiogenesis and lymph node metastasis in head and neck cancer. Cancer Res. 62:1315–20 [Google Scholar]
  88. Kyzas PA, Geleff S, Batistatou A, Agnantis NJ, Stefanou D. 88.  2005. Evidence for lymphangiogenesis and its prognostic implications in head and neck squamous cell carcinoma. J. Pathol. 206:170–77 [Google Scholar]
  89. Shields JD, Emmett MS, Dunn DB, Joory KD, Sage LM. 89.  et al. 2007. Chemokine-mediated migration of melanoma cells towards lymphatics—a mechanism contributing to metastasis. Oncogene 26:2997–3005 [Google Scholar]
  90. Seeger H, Bonani M, Segerer S. 90.  2012. The role of lymphatics in renal inflammation. Nephrol. Dial. Transplant. 27:2634–41 [Google Scholar]
  91. Pober JS, Sessa WC. 91.  2007. Evolving functions of endothelial cells in inflammation. Nat. Rev. Immunol. 7:803–15 [Google Scholar]
  92. Clark PR, Manes TD, Pober JS, Kluger MS. 92.  2007. Increased ICAM-1 expression causes endothelial cell leakiness, cytoskeletal reorganization and junctional alterations. J. Investig. Dermatol. 127:762–74 [Google Scholar]
  93. Adams DH, Shaw S. 93.  1994. Leucocyte-endothelial interactions and regulation of leucocyte migration. Lancet 343:831–36 [Google Scholar]
  94. Meroni PL, Khamashta MA, Youinou P, Shoenfeld Y. 94.  1995. Mosaic of anti-endothelial antibodies: review of the first international workshop on anti-endothelial antibodies: clinical and pathological significance: Milan, 9 November 1994. Lupus 4:95–99 [Google Scholar]
  95. Hunt BJ, Jurd KM. 95.  1998. Endothelial cell activation: a central pathophysiological process. BMJ 316:1328–29 [Google Scholar]
  96. Bierhaus A, Chevion S, Chevion M, Hofmann M, Quehenberger P. 96.  et al. 1997. Advanced glycation end product-induced activation of NF-κB is suppressed by α-lipoic acid in cultured endothelial cells. Diabetes 46:1481–90 [Google Scholar]
  97. Middleton J, Neil S, Wintle J, Clark-Lewis I, Moore H. 97.  et al. 1997. Transcytosis and surface presentation of IL-8 by venular endothelial cells. Cell 91:385–95 [Google Scholar]
  98. Pober JS, Orosz CG, Rose ML, Savage CO. 98.  1996. Can graft endothelial cells initiate a host anti-graft immune response?. Transplantation 61:343–49 [Google Scholar]
  99. Shiao SL, McNiff JM, Pober JS. 99.  2005. Memory T cells and their costimulators in human allograft injury. J. Immunol. 175:4886–96 [Google Scholar]
  100. Barone F, Bombardieri M, Manzo A, Blades MC, Morgan PR. 100.  et al. 2005. Association of CXCL13 and CCL21 expression with the progressive organization of lymphoid-like structures in Sjögren's syndrome. Arthritis Rheum. 52:1773–84 [Google Scholar]
  101. Manzo A, Paoletti S, Carulli M, Blades MC, Barone F. 101.  et al. 2005. Systematic microanatomical analysis of CXCL13 and CCL21 in situ production and progressive lymphoid organization in rheumatoid synovitis. Eur. J. Immunol. 35:1347–59 [Google Scholar]
  102. Girard JP, Springer TA. 102.  1995. High endothelial venules (HEVs): specialized endothelium for lymphocyte migration. Immunol. Today 16:449–57 [Google Scholar]
  103. Carragher D, Johal R, Button A, White A, Eliopoulos A. 103.  et al. 2004. A stroma-derived defect in NF-κB2−/− mice causes impaired lymph node development and lymphocyte recruitment. J. Immunol. 173:2271–79 [Google Scholar]
  104. Browning JL, Allaire N, Ngam-ek A, Notidis E, Hunt J. 104.  et al. 2005. Lymphotoxin-β receptor signaling is required for the homeostatic control of HEV differentiation and function. Immunity 23:539–50 [Google Scholar]
  105. Onder L, Danuser R, Scandella E, Firner S, Chai Q. 105.  et al. 2013. Endothelial cell–specific lymphotoxin-β receptor signaling is critical for lymph node and high endothelial venule formation. J. Exp. Med. 210:465–73 [Google Scholar]
  106. Costa C, Incio J, Soares R. 106.  2007. Angiogenesis and chronic inflammation: cause or consequence?. Angiogenesis 10:149–66 [Google Scholar]
  107. Helmlinger G, Yuan F, Dellian M, Jain RK. 107.  1997. Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation. Nat. Med. 3:177–82 [Google Scholar]
  108. Eberhard A, Kahlert S, Goede V, Hemmerlein B, Plate KH. 108.  et al. 2000. Heterogeneity of angiogenesis and blood vessel maturation in human tumors: implications for antiangiogenic tumor therapies. Cancer Res. 60:1388–93 [Google Scholar]
  109. Eliceiri BP, Cheresh DA. 109.  1999. The role of αv integrins during angiogenesis: insights into potential mechanisms of action and clinical development. J. Clin. Investig. 103:1227–30 [Google Scholar]
  110. Taylor PC, Sivakumar B. 110.  2005. Hypoxia and angiogenesis in rheumatoid arthritis. Curr. Opin. Rheumatol. 17:293–98 [Google Scholar]
  111. Kim D, Mebius RE, MacMicking JD, Jung S, Cupedo T. 111.  et al. 2000. Regulation of peripheral lymph node genesis by the tumor necrosis factor family member TRANCE. J. Exp. Med. 192:1467–78 [Google Scholar]
  112. Dougall WC, Glaccum M, Charrier K, Rohrbach K, Brasel K. 112.  et al. 1999. RANK is essential for osteoclast and lymph node development. Genes Dev. 13:2412–24 [Google Scholar]
  113. Eberl G, Marmon S, Sunshine MJ, Rennert PD, Choi Y. 113.  et al. 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]
  114. Yokota Y, Mansouri A, Mori S, Sugawara S, Adachi S. 114.  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]
  115. Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E. 115.  et al. 1999. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 397:315–23 [Google Scholar]
  116. van de Pavert SA, Olivier BJ, Goverse G, Vondenhoff MF, Greuter M. 116.  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]
  117. Luther SA, Ansel KM, Cyster JG. 117.  2003. Overlapping roles of CXCL13, interleukin 7 receptor α, and CCR7 ligands in lymph node development. J. Exp. Med. 197:1191–98 [Google Scholar]
  118. Cupedo T, Kraal G, Mebius RE. 118.  2002. The role of CD45+CD4+CD3 cells in lymphoid organ development. Immunol. Rev. 189:41–50 [Google Scholar]
  119. Cupedo T, Mebius RE. 119.  2005. Cellular interactions in lymph node development. J. Immunol. 174:21–25 [Google Scholar]
  120. Naito A, Azuma S, Tanaka S, Miyazaki T, Takaki S. 120.  et al. 1999. Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice. Genes Cells 4:353–62 [Google Scholar]
  121. Vondenhoff MF, Greuter M, Goverse G, Elewaut D, Dewint P. 121.  et al. 2009. LTβR signaling induces cytokine expression and up-regulates lymphangiogenic factors in lymph node anlagen. J. Immunol. 182:5439–45 [Google Scholar]
  122. Dejardin E, Droin NM, Delhase M, Haas E, Cao Y. 122.  et al. 2002. The lymphotoxin-β receptor induces different patterns of gene expression via two NF-κB pathways. Immunity 17:525–35 [Google Scholar]
  123. Ansel KM, Ngo VN, Hyman PL, Luther SA, Forster R. 123.  et al. 2000. A chemokine-driven positive feedback loop organizes lymphoid follicles. Nature 406:309–14 [Google Scholar]
  124. White A, Carragher D, Parnell S, Msaki A, Perkins N. 124.  et al. 2007. Lymphotoxin a-dependent and -independent signals regulate stromal organizer cell homeostasis during lymph node organogenesis. Blood 110:1950–59 [Google Scholar]
  125. Bénézech C, White A, Mader E, Serre K, Parnell S. 125.  et al. 2010. Ontogeny of stromal organizer cells during lymph node development. J. Immunol. 184:4521–30 [Google Scholar]
  126. Cupedo T, Vondenhoff MF, Heeregrave EJ, De Weerd AE, Jansen W. 126.  et al. 2004. Presumptive lymph node organizers are differentially represented in developing mesenteric and peripheral nodes. J. Immunol. 173:2968–75 [Google Scholar]
  127. Bénézech C, Mader E, Desanti G, Khan M, Nakamura K. 127.  et al. 2012. Lymphotoxin-β receptor signaling through NF-κB2-RelB pathway reprograms adipocyte precursors as lymph node stromal cells. Immunity 37:721–34 [Google Scholar]
  128. Ruddle NH, Akirav EM. 128.  2009. Secondary lymphoid organs: responding to genetic and environmental cues in ontogeny and the immune response. J. Immunol. 183:2205–12 [Google Scholar]
  129. Roozendaal R, Mebius RE. 129.  2011. Stromal cell–immune cell interactions. Annu. Rev. Immunol. 29:23–43 [Google Scholar]
  130. Katakai T, Hara T, Sugai M, Gonda H, Shimizu A. 130.  2004. Lymph node fibroblastic reticular cells construct the stromal reticulum via contact with lymphocytes. J. Exp. Med. 200:783–95 [Google Scholar]
  131. Chai Q, Onder L, Scandella E, Gil-Cruz C, Perez-Shibayama C. 131.  et al. 2013. Maturation of lymph node fibroblastic reticular cells from myofibroblastic precursors is critical for antiviral immunity. Immunity 38:1013–24 [Google Scholar]
  132. Luther SA, Tang HL, Hyman PL, Farr AG, Cyster JG. 132.  2000. Coexpression of the chemokines ELC and SLC by T zone stromal cells and deletion of the ELC gene in the plt/plt mouse. PNAS 97:12694–99 [Google Scholar]
  133. Link A, Vogt TK, Favre S, Britschgi MR, Acha-Orbea H. 133.  et al. 2007. Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells. Nat. Immunol. 8:1255–65 [Google Scholar]
  134. Cyster JG, Ansel KM, Reif K, Ekland EH, Hyman PL. 134.  et al. 2000. Follicular stromal cells and lymphocyte homing to follicles. Immunol. Rev. 176:181–93 [Google Scholar]
  135. Jarjour M, Jorquera A, Mondor I, Wienert S, Narang P. 135.  et al. 2014. Fate mapping reveals origin and dynamics of lymph node follicular dendritic cells. J. Exp. Med. 211:1109–22 [Google Scholar]
  136. Mionnet C, Mondor I, Jorquera A, Loosveld M, Maurizio J. 136.  et al. 2013. Identification of a new stromal cell type involved in the regulation of inflamed B cell follicles. PLOS Biol. 11:e1001672 [Google Scholar]
  137. Moussion C, Girard JP. 137.  2011. Dendritic cells control lymphocyte entry to lymph nodes through high endothelial venules. Nature 479:542–46 [Google Scholar]
  138. Wendland M, Willenzon S, Kocks J, Davalos-Misslitz AC, Hammerschmidt SI. 138.  et al. 2011. Lymph node T cell homeostasis relies on steady state homing of dendritic cells. Immunity 35:945–57 [Google Scholar]
  139. Sixt M, Kanazawa N, Selg M, Samson T, Roos G. 139.  et al. 2005. The conduit system transports soluble antigens from the afferent lymph to resident dendritic cells in the T cell area of the lymph node. Immunity 22:19–29 [Google Scholar]
  140. Bajenoff M, Germain RN. 140.  2009. B-cell follicle development remodels the conduit system and allows soluble antigen delivery to follicular dendritic cells. Blood 114:4989–97 [Google Scholar]
  141. Bajénoff M, Egen JG, Koo LY, Laugier JP, Brau F. 141.  et al. 2006. Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes. Immunity 25:989–1001 [Google Scholar]
  142. Mueller SN, Germain RN. 142.  2009. Stromal cell contributions to the homeostasis and functionality of the immune system. Nat. Rev. Immunol. 9:618–29 [Google Scholar]
  143. Roozendaal R, Mempel TR, Pitcher LA, Gonzalez SF, Verschoor A. 143.  et al. 2009. Conduits mediate transport of low-molecular-weight antigen to lymph node follicles. Immunity 30:264–76 [Google Scholar]
  144. Lochner M, Ohnmacht C, Presley L, Bruhns P, Si-Tahar M. 144.  et al. 2010. Microbiota-induced tertiary lymphoid tissues aggravate inflammatory disease in the absence of RORγt and LTi cells. J. Exp. Med. 208:125–34 [Google Scholar]
  145. Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T. 145.  et al. 2010. Innate production of TH2 cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphoid cells. Nature 463:540–44 [Google Scholar]
  146. Tsuji M, Suzuki K, Kitamura H, Maruya M, Kinoshita K. 146.  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]
  147. Rangel-Moreno J, Carragher DM, de la Luz Garcia-Hernandez M, Hwang JY, Kusser K. 147.  et al. 2011. The development of inducible bronchus-associated lymphoid tissue depends on IL-17. Nat. Immunol. 12:639–46 [Google Scholar]
  148. Fukuyama S, Hiroi T, Yokota Y, Rennert PD, Yanagita M. 148.  et al. 2002. Initiation of NALT organogenesis is independent of the IL-7R, LTβR, and NIK signaling pathways but requires the Id2 gene and CD3CD4+CD45+ cells. Immunity 17:31–40 [Google Scholar]
  149. Harmsen A, Kusser K, Hartson L, Tighe M, Sunshine MJ. 149.  et al. 2002. Cutting edge: organogenesis of nasal-associated lymphoid tissue (NALT) occurs independently of lymphotoxin-α (LTα) and retinoic acid receptor-related orphan receptor-γ, but the organization of NALT is LTα dependent. J. Immunol. 168:986–90 [Google Scholar]
  150. Nagatake T, Fukuyama S, Kim DY, Goda K, Igarashi O. 150.  et al. 2009. Id2-, RORγt-, and LTβR-independent initiation of lymphoid organogenesis in ocular immunity. J. Exp. Med. 206:2351–64 [Google Scholar]
  151. GeurtsvanKessel CH, Willart MA, Bergen IM, van Rijt LS, Muskens F. 151.  et al. 2009. Dendritic cells are crucial for maintenance of tertiary lymphoid structures in the lung of influenza virus–infected mice. J. Exp. Med. 206:2339–49 [Google Scholar]
  152. Fleige H, Ravens S, Moschovakis GL, Bolter J, Willenzon S. 152.  et al. 2014. IL-17-induced CXCL12 recruits B cells and induces follicle formation in BALT in the absence of differentiated FDCs. J. Exp. Med. 211:643–51 [Google Scholar]
  153. Moyron-Quiroz JE, Rangel-Moreno J, Kusser K, Hartson L, Sprague F. 153.  et al. 2004. Role of inducible bronchus associated lymphoid tissue (iBALT) in respiratory immunity. Nat. Med. 10:927–34 [Google Scholar]
  154. Rangel-Moreno J, Moyron-Quiroz JE, Carragher DM, Kusser K, Hartson L. 154.  et al. 2009. Omental milky spots develop in the absence of lymphoid tissue-inducer cells and support B and T cell responses to peritoneal antigens. Immunity 30:731–43 [Google Scholar]
  155. Carragher DM, Rangel-Moreno J, Randall TD. 155.  2008. Ectopic lymphoid tissues and local immunity. Semin. Immunol. 20:26–42 [Google Scholar]
  156. Mittal S, Revell M, Barone F, Hardie DL, Matharu GS. 156.  et al. 2013. Lymphoid aggregates that resemble tertiary lymphoid organs define a specific pathological subset in metal-on-metal hip replacements. PLOS ONE 8:e63470 [Google Scholar]
  157. Neyt K, Perros F, GeurtsvanKessel CH, Hammad H, Lambrecht BN. 157.  2012. Tertiary lymphoid organs in infection and autoimmunity. Trends Immunol. 33:297–305 [Google Scholar]
  158. Drayton DL, Liao S, Mounzer RH, Ruddle NH. 158.  2006. Lymphoid organ development: from ontogeny to neogenesis. Nat. Immunol. 7:344–53 [Google Scholar]
  159. Aust G, Sittig D, Becherer L, Anderegg U, Schütz A. 159.  et al. 2004. The role of CXCR5 and its ligand CXCL13 in the compartmentalization of lymphocytes in thyroids affected by autoimmune thyroid diseases. Eur. J. Endocrinol. 150:225–34 [Google Scholar]
  160. Söderström N, Blörklund A. 160.  1974. Organization of the invading lymphoid tissue in human lymphoid thyroiditis. Scand. J. Immunol. 3:295–301 [Google Scholar]
  161. Armengol MP, Juan M, Lucas-Martin A, Fernández-Figueras MT, Jaraquemada D. 161.  et al. 2001. Thyroid autoimmune disease: demonstration of thyroid antigen-specific B cells and recombination-activating gene expression in chemokine-containing active intrathyroidal germinal centers. Am. J. Pathol. 159:861–73 [Google Scholar]
  162. Armengol MP, Cardoso-Schmidt CB, Fernández M, Ferrer X, Pujol-Borrell R, Juan M. 162.  2003. Chemokines determine local lymphoneogenesis and a reduction of circulating CXCR4+ T and CCR7 B and T lymphocytes in thyroid autoimmune diseases. J. Immunol. 170:6320–28 [Google Scholar]
  163. Drumea-Mirancea M, Wessels JT, Muller CA, Essl M, Eble JA. 163.  et al. 2006. Characterization of a conduit system containing laminin-5 in the human thymus: a potential transport system for small molecules. J. Cell Sci. 119:1396–405 [Google Scholar]
  164. Link A, Hardie DL, Favre S, Britschgi MR, Adams DH. 164.  et al. 2011. Association of T-zone reticular networks and conduits with ectopic lymphoid tissues in mice and humans. Am. J. Pathol. 178:1662–75 [Google Scholar]
  165. Takemura S, Braun A, Crowson C, Kurtin PJ, Cofield RH. 165.  et al. 2001. Lymphoid neogenesis in rheumatoid synovitis. J. Immunol. 167:1072–80 [Google Scholar]
  166. Rangel-Moreno J, Hartson L, Navarro C, Gaxiola M, Selman M. 166.  et al. 2006. Inducible bronchus-associated lymphoid tissue (iBALT) in patients with pulmonary complications of rheumatoid arthritis. J. Clin. Investig. 116:3183–94 [Google Scholar]
  167. Amft N, Curnow SJ, Scheel-Toellner D, Devadas A, Oates J. 167.  et al. 2001. Ectopic expression of the B cell–attracting chemokine BCA-1 (CXCL13) on endothelial cells and within lymphoid follicles contributes to the establishment of germinal center–like structures in Sjögren's syndrome. Arthritis Rheum. 44:2633–41 [Google Scholar]
  168. Hjelmstrom P, Fjell J, Nakagawa T, Sacca R, Cuff CA. 168.  et al. 2000. Lymphoid tissue homing chemokines are expressed in chronic inflammation. Am. J. Pathol. 156:1133–38 [Google Scholar]
  169. Hjelmstrom P. 169.  2001. Lymphoid neogenesis: de novo formation of lymphoid tissue in chronic inflammation through expression of homing chemokines. J. Leukoc. Biol. 69:331–39 [Google Scholar]
  170. Phillips RJ, Burdick MD, Hong K, Lutz MA, Murray LA. 170.  et al. 2004. Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis. J. Clin. Investig. 114:438–46 [Google Scholar]
  171. Weyand CM, Goronzy JJ. 171.  2003. Ectopic germinal center formation in rheumatoid synovitis. Ann. N.Y. Acad. Sci. 987:140–49 [Google Scholar]
  172. Manzo A, Bombardieri M, Humby F, Pitzalis C. 172.  2010. Secondary and ectopic lymphoid tissue responses in rheumatoid arthritis: from inflammation to autoimmunity and tissue damage/remodeling. Immunol. Rev. 233:267–85 [Google Scholar]
  173. Salomonsson S, Larsson P, Tengnér P, Mellquist E, Hjelmström P, Wahren-Herlenius M. 173.  2002. Expression of the B cell-attracting chemokine CXCL13 in the target organ and autoantibody production in ectopic lymphoid tissue in the chronic inflammatory disease Sjögren's syndrome. Scand. J. Immunol. 55:336–42 [Google Scholar]
  174. Klimiuk PA, Sierakowski S, Latosiewicz R, Cylwik JP, Cylwik B. 174.  et al. 2003. Circulating tumour necrosis factor α and soluble tumour necrosis factor receptors in patients with different patterns of rheumatoid synovitis. Ann. Rheum. Dis. 62:472–75 [Google Scholar]
  175. Klimiuk PA, Sierakowski S, Latosiewicz R, Cylwik B, Skowronski J. 175.  et al. 2001. Serum cytokines in different histological variants of rheumatoid arthritis. J. Rheumatol. 28:1211–17 [Google Scholar]
  176. de Hair MJ, van de Sande MG, Ramwadhdoebe TH, Hansson M, Landewe R. 176.  et al. 2014. Features of the synovium of individuals at risk of developing rheumatoid arthritis: implications for understanding preclinical rheumatoid arthritis. Arthritis Rheumatol. 66:513–22 [Google Scholar]
  177. Bugatti S, Manzo A, Benaglio F, Klersy C, Vitolo B. 177.  et al. 2012. Serum levels of CXCL13 are associated with ultrasonographic synovitis and predict power Doppler persistence in early rheumatoid arthritis treated with non-biological disease-modifying anti-rheumatic drugs. Arthritis Res. Ther. 14:R34 [Google Scholar]
  178. Bugatti S, Caporali R, Manzo A, Vitolo B, Pitzalis C. 178.  et al. 2005. Involvement of subchondral bone marrow in rheumatoid arthritis: lymphoid neogenesis and in situ relationship to subchondral bone marrow osteoclast recruitment. Arthritis Rheum. 52:3448–59 [Google Scholar]
  179. Wotherspoon AC, Doglioni C, Diss TC, Pan L, Moschini A. 179.  et al. 1993. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet 342:575–77 [Google Scholar]
  180. Barone F, Bombardieri M, Rosado MM, Morgan PR, Challacombe SJ. 180.  et al. 2008. CXCL13, CCL21, and CXCL12 expression in salivary glands of patients with Sjögren's syndrome and MALT lymphoma: association with reactive and malignant areas of lymphoid organization. J. Immunol. 180:5130–40 [Google Scholar]
  181. Xanthou G, Polihronis M, Tzioufas AG, Paikos S, Sideras P. 181.  et al. 2001. “Lymphoid” chemokine messenger RNA expression by epithelial cells in the chronic inflammatory lesion of the salivary glands of Sjögren's syndrome patients: possible participation in lymphoid structure formation. Arthritis Rheum. 44:408–18 [Google Scholar]
  182. Pitzalis C, Jones GW, Bombardieri M, Jones SA. 182.  2014. Ectopic lymphoid-like structures in infection, cancer and autoimmunity. Nat. Rev. Immunol. 14:447–62 [Google Scholar]
  183. Quartuccio L, Fabris M, Moretti M, Barone F, Bombardieri M. 183.  et al. 2008. Resistance to rituximab therapy and local BAFF overexpression in Sjögren's syndrome-related myoepithelial sialadenitis and low-grade parotid B-cell lymphoma. Open Rheumatol. J. 2:38–43 [Google Scholar]
  184. Kratz A, Campos-Neto A, Hanson MS, Ruddle NH. 184.  1996. Chronic inflammation caused by lymphotoxin is lymphoid neogenesis. J. Exp. Med. 183:1461–72 [Google Scholar]
  185. Picarella DE, Kratz A, Li CB, Ruddle NH, Flavell RA. 185.  1993. Transgenic tumor necrosis factor (TNF)-alpha production in pancreatic islets leads to insulitis, not diabetes. Distinct patterns of inflammation in TNF-alpha and TNF-beta transgenic mice. J. Immunol. 150:4136–50 [Google Scholar]
  186. Sacca R, Kratz A, Campos-Neto A, Hanson MS, Ruddle NH. 186.  1995. Lymphotoxin: from chronic inflammation to lymphoid organs. J. Inflamm. 47:81–84 [Google Scholar]
  187. Drayton DL, Ying X, Lee J, Lesslauer W, Ruddle NH. 187.  2003. Ectopic LTαβ directs lymphoid organ neogenesis with concomitant expression of peripheral node addressin and a HEV-restricted sulfotransferase. J. Exp. Med. 197:1153–63 [Google Scholar]
  188. Luther SA, Lopez T, Bai W, Hanahan D, Cyster JG. 188.  2000. BLC expression in pancreatic islets causes B cell recruitment and lymphotoxin-dependent lymphoid neogenesis. Immunity 12:471–81 [Google Scholar]
  189. Chen SC, Vassileva G, Kinsley D, Holzmann S, Manfra D. 189.  et al. 2002. Ectopic expression of the murine chemokines CCL21a and CCL21b induces the formation of lymph node-like structures in pancreas, but not skin, of transgenic mice. J. Immunol. 168:1001–8 [Google Scholar]
  190. Fan L, Reilly CR, Luo Y, Dorf ME, Lo D. 190.  2000. Cutting edge: ectopic expression of the chemokine TCA4/SLC is sufficient to trigger lymphoid neogenesis. J. Immunol. 164:3955–59 [Google Scholar]
  191. Lira SA, Martin AP, Marinkovic T, Furtado GC. 191.  2005. Mechanisms regulating lymphocytic infiltration of the thyroid in murine models of thyroiditis. Crit. Rev. Immunol. 25:251–62 [Google Scholar]
  192. Furtado GC, Marinkovic T, Martin AP, Garin A, Hoch B. 192.  et al. 2007. Lymphotoxin β receptor signaling is required for inflammatory lymphangiogenesis in the thyroid. PNAS 104:5026–31 [Google Scholar]
  193. Luther SA, Bidgol A, Hargreaves DC, Schmidt A, Xu Y. 193.  et al. 2002. Differing activities of homeostatic chemokines CCL19, CCL21, and CXCL12 in lymphocyte and dendritic cell recruitment and lymphoid neogenesis. J. Immunol. 169:424–33 [Google Scholar]
  194. Peters A, Pitcher LA, Sullivan JM, Mitsdoerffer M, Acton SE. 194.  et al. 2011. Th17 cells induce ectopic lymphoid follicles in central nervous system tissue inflammation. Immunity 35:986–96 [Google Scholar]
  195. Schrama D, thor Straten P, Fischer WH, McLellan AD, Brocker EB. 195.  et al. 2001. Targeting of lymphotoxin-α to the tumor elicits an efficient immune response associated with induction of peripheral lymphoid-like tissue. Immunity 14:111–21 [Google Scholar]
  196. Yu P, Lee Y, Liu W, Chin RK, Wang J. 196.  et al. 2004. Priming of naive T cells inside tumors leads to eradication of established tumors. Nat. Immunol. 5:141–49 [Google Scholar]
  197. Astorri E, Bombardieri M, Gabba S, Peakman M, Pozzilli P. 197.  et al. 2010. Evolution of ectopic lymphoid neogenesis and in situ autoantibody production in autoimmune nonobese diabetic mice: cellular and molecular characterization of tertiary lymphoid structures in pancreatic islets. J. Immunol. 185:3359–68 [Google Scholar]
  198. Bombardieri M, Barone F, Humby F, Kelly S, McGurk M. 198.  et al. 2007. Activation-induced cytidine deaminase expression in follicular dendritic cell networks and interfollicular large B cells supports functionality of ectopic lymphoid neogenesis in autoimmune sialoadenitis and MALT lymphoma in Sjögren's syndrome. J. Immunol. 179:4929–38 [Google Scholar]
  199. Gräbner R, Lötzer K, Döpping S, Hildner M, Radke D. 199.  et al. 2009. Lymphotoxin β receptor signaling promotes tertiary lymphoid organogenesis in the aorta adventitia of aged ApoE−/− mice. J. Exp. Med. 206:233–48 [Google Scholar]
  200. Lötzer K, Döpping S, Connert S, Gräbner R, Spanbroek R. 200.  et al. 2010. Mouse aorta smooth muscle cells differentiate into lymphoid tissue organizer-like cells on combined tumor necrosis factor receptor-1/lymphotoxin β-receptor NF-κB signaling. Arterioscler. Thromb. Vasc. Biol. 30:395–402 [Google Scholar]
  201. Wengner AM, Höpken UE, Petrow PK, Hartmann S, Schurigt U. 201.  et al. 2007. CXCR5- and CCR7-dependent lymphoid neogenesis in a murine model of chronic antigen-induced arthritis. Arthritis Rheumatol 56:3271–83 [Google Scholar]
  202. Barone F, Nayar S, Buckley CD. 202.  2012. The role of non-hematopoietic stromal cells in the persistence of inflammation. Front. Immunol. 3:416 [Google Scholar]
  203. Cupedo T, Jansen W, Kraal G, Mebius RE. 203.  2004. Induction of secondary and tertiary lymphoid structures in the skin. Immunity 21:655–67 [Google Scholar]
  204. Suematsu S, Watanabe T. 204.  2004. Generation of a synthetic lymphoid tissue–like organoid in mice. Nat. Biotechnol. 22:1539–45 [Google Scholar]
  205. Peduto L, Dulauroy S, Lochner M, Spath GF, Morales MA. 205.  et al. 2009. Inflammation recapitulates the ontogeny of lymphoid stromal cells. J. Immunol. 182:5789–99 [Google Scholar]
  206. Krautler NJ, Kana V, Kranich J, Tian Y, Perera D. 206.  et al. 2012. Follicular dendritic cells emerge from ubiquitous perivascular precursors. Cell 150:194–206 [Google Scholar]
  207. Abe J, Shichino S, Ueha S, Hashimoto S, Tomura M. 207.  et al. 2014. Lymph node stromal cells negatively regulate antigen-specific CD4+ T cell responses. J. Immunol. 193:1636–44 [Google Scholar]
  208. Yang CY, Vogt TK, Favre S, Scarpellino L, Huang HY. 208.  et al. 2014. Trapping of naive lymphocytes triggers rapid growth and remodeling of the fibroblast network in reactive murine lymph nodes. PNAS 111:E109–18 [Google Scholar]
  209. Scandella E, Bolinger B, Lattmann E, Miller S, Favre S. 209.  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]
  210. Mueller SN, Matloubian M, Clemens DM, Sharpe AH, Freeman GJ. 210.  et al. 2007. Viral targeting of fibroblastic reticular cells contributes to immunosuppression and persistence during chronic infection. PNAS 104:15430–35 [Google Scholar]
  211. Castagnaro L, Lenti E, Maruzzelli S, Spinardi L, Migliori E. 211.  et al. 2013. Nkx2-5+Islet1+ mesenchymal precursors generate distinct spleen stromal cell subsets and participate in restoring stromal network integrity. Immunity 38:782–91 [Google Scholar]
  212. Denton AE, Roberts EW, Linterman MA, Fearon DT. 212.  2014. Fibroblastic reticular cells of the lymph node are required for retention of resting but not activated CD8+ T cells. PNAS 111:12139–44 [Google Scholar]
  213. Junt T, Scandella E, Ludewig B. 213.  2008. Form follows function: lymphoid tissue microarchitecture in antimicrobial immune defence. Nat. Rev. Immunol. 8:764–75 [Google Scholar]
  214. Cremasco V, Woodruff MC, Onder L, Cupovic J, Nieves-Bonilla JM. 214.  et al. 2014. B cell homeostasis and follicle confines are governed by fibroblastic reticular cells. Nat. Immunol. 15:973–81 [Google Scholar]
  215. Gardner JM, Devoss JJ, Friedman RS, Wong DJ, Tan YX. 215.  et al. 2008. Deletional tolerance mediated by extrathymic Aire-expressing cells. Science 321:843–47 [Google Scholar]
  216. Lee JW, Epardaud M, Sun J, Becker JE, Cheng AC. 216.  et al. 2007. Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self. Nat. Immunol. 8:181–90 [Google Scholar]
  217. Fletcher AL, Lukacs-Kornek V, Reynoso ED, Pinner SE, Bellemare-Pelletier A. 217.  et al. 2010. Lymph node fibroblastic reticular cells directly present peripheral tissue antigen under steady-state and inflammatory conditions. J. Exp. Med. 207:689–97 [Google Scholar]
  218. Dubrot J, Duraes FV, Potin L, Capotosti F, Brighouse D. 218.  et al. 2014. Lymph node stromal cells acquire peptide–MHCII complexes from dendritic cells and induce antigen-specific CD4+ T cell tolerance. J. Exp. Med. 211:1153–66 [Google Scholar]
  219. Baptista AP, Roozendaal R, Reijmers RM, Koning JJ, Unger WW. 219.  et al. 2014. Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation. eLIFE 3:e04433 [Google Scholar]
  220. Lukacs-Kornek V, Malhotra D, Fletcher AL, Acton SE, Elpek KG. 220.  et al. 2011. Regulated release of nitric oxide by nonhematopoietic stroma controls expansion of the activated T cell pool in lymph nodes. Nat. Immunol. 12:1096–104 [Google Scholar]
  221. Siegert S, Huang HY, Yang CY, Scarpellino L, Carrie L. 221.  et al. 2011. Fibroblastic reticular cells from lymph nodes attenuate T cell expansion by producing nitric oxide. PLOS ONE 6:e27618 [Google Scholar]
  222. Khan O, Headley M, Gerard A, Wei W, Liu L. 222.  et al. 2011. Regulation of T cell priming by lymphoid stroma. PLOS ONE 6:e26138 [Google Scholar]
  223. Hammerschmidt SI, Ahrendt M, Bode U, Wahl B, Kremmer E. 223.  et al. 2008. Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo. J. Exp. Med. 205:2483–90 [Google Scholar]
  224. Molenaar R, Greuter M, van der Marel AP, Roozendaal R, Martin SF. 224.  et al. 2009. Lymph node stromal cells support dendritic cell-induced gut-homing of T cells. J. Immunol. 183:6395–402 [Google Scholar]
  225. Vicente-Suarez I, Larange A, Reardon C, Matho M, Feau S. 225.  et al. 2015. Unique lamina propria stromal cells imprint the functional phenotype of mucosal dendritic cells. Mucosal Immunol. 8:141–51 [Google Scholar]
  226. Iliev ID, Mileti E, Matteoli G, Chieppa M, Rescigno M. 226.  2009. Intestinal epithelial cells promote colitis-protective regulatory T-cell differentiation through dendritic cell conditioning. Mucosal Immunol. 2:340–50 [Google Scholar]
  227. Furtado GC, Pacer ME, Bongers G, Bénézech C, He Z. 227.  et al. 2014. TNFα-dependent development of lymphoid tissue in the absence of RORγt+ lymphoid tissue inducer cells. Mucosal Immunol. 7:602–14 [Google Scholar]
  228. Marinkovic T. 228.  2006. Interaction of mature CD3+CD4+ T cells with dendritic cells triggers the development of tertiary lymphoid structures in the thyroid. J. Clin. Investig. 116:2622–32 [Google Scholar]
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