Gastroenterology
Volume 137, Issue 5 , Pages 1736-1745 , November 2009

Th1/Th17 Immune Response Is Induced by Mesenteric Lymph Node Dendritic Cells in Crohn's Disease

  • Atsushi Sakuraba

      Affiliations

    • Division of Gastroenterology, Department of Internal Medicine, Keio University School of Medicine, Tokyo
    • ,
  • Toshiro Sato

      Affiliations

    • Division of Gastroenterology, Department of Internal Medicine, Keio University School of Medicine, Tokyo
    • ,
  • Nobuhiko Kamada

      Affiliations

    • Division of Gastroenterology, Department of Internal Medicine, Keio University School of Medicine, Tokyo
    • ,
  • Mina Kitazume

      Affiliations

    • Division of Gastroenterology, Department of Internal Medicine, Keio University School of Medicine, Tokyo
    • ,
  • Akira Sugita

      Affiliations

    • Department of Surgery, Yokohama Municipal Hospital, Yokohama, Japan
    • ,
  • Toshifumi Hibi

      Affiliations

    • Division of Gastroenterology, Department of Internal Medicine, Keio University School of Medicine, Tokyo
    • Corresponding Author InformationReprint requests Address requests for reprints to: Toshifumi Hibi, MD, PhD, Division of Gastroenterology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. fax: (81) 3-3357-6156

Received 22 October 2008 ,Accepted 16 July 2009.

References 

  1. Podolsky DK. Inflammatory bowel disease. N Engl J Med. 2002;347:417–429
  2. Takagi H, Kanai T, Okazawa A, et al. Contrasting action of IL-12 and IL-18 in the development of dextran sodium sulphate colitis in mice. Scand J Gastroenterol. 2003;38:837–844
  3. Okazawa A, Kanai T, Watanabe M, et al. Th1-mediated intestinal inflammation in Crohn's disease may be induced by activation of lamina propria lymphocytes through synergistic stimulation of interleukin-12 and interleukin-18 without T-cell receptor engagement. Am J Gastroenterol. 2002;97:3108–3117
  4. Kanai T, Watanabe M, Okazawa A, et al. Interleukin 18 is a potent proliferative factor for intestinal mucosal lymphocytes in Crohn's disease. Gastroenterology. 2000;119:1514–1523
  5. Matsuoka K, Inoue N, Sato T, et al. T-bet up-regulation and subsequent interleukin 12 stimulation are essential for induction of Th1-mediated immunopathology in Crohn's disease. Gut. 2004;53:1303–1308
  6. Monteleone G, Biancone L, Marasco R, et al. Interleukin 12 is expressed and actively released by Crohn's disease intestinal lamina propria mononuclear cells. Gastroenterology. 1997;112:1169–1178
  7. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392:245–252
  8. Banchereau J, Briere F, Caux C, et al. Immunobiology of dendritic cells. Annu Rev Immunol. 2000;18:767–811
  9. Rescigno M, Urbano M, Valzasina B, et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol. 2001;2:361–367
  10. Niess JH, Brand S, Gu X, et al. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science. 2005;307:254–258
  11. Kobayashi H, Miura S, Nagata H, et al. In situ demonstration of dendritic cell migration from rat intestine to mesenteric lymph nodes: relationships to maturation and role of chemokines. J Leukoc Biol. 2004;75:434–442
  12. Inaba K, Witmer-Pack M, Inaba M, et al. The tissue distribution of the B7-2 costimulator in mice: abundant expression on dendritic cells in situ and during maturation in vitro. J Exp Med. 1994;180:1849–1860
  13. Inaba K, Inaba M, Witmer-Pack M, et al. Expression of B7 costimulator molecules on mouse dendritic cells. Adv Exp Med Biol. 1995;378:65–70
  14. Caux C, Vanbervliet B, Massacrier C, et al. B70/B7-2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells. J Exp Med. 1994;180:1841–1847
  15. Young JW, Koulova L, Soergel SA, et al. The B7/BB1 antigen provides one of several costimulatory signals for the activation of CD4+ T lymphocytes by human blood dendritic cells in vitro. J Clin Invest. 1992;90:229–237
  16. Kalinski P, Moser M. Consensual immunity: success-driven development of T-helper 1 and T-helper 2 responses. Nat Rev Immunol. 2005;5:251–260
  17. Rissoan MC, Soumelis V, Kadowaki N, et al. Reciprocal control of T helper cell and dendritic cell differentiation. Science. 1999;283:1183–1186
  18. Ingulli E, Ulman DR, Lucido MM, et al. In situ analysis reveals physical interactions between CD11b+ dendritic cells and antigen-specific CD4 T cells after subcutaneous injection of antigen. J Immunol. 2002;169:2247–2252
  19. Cella M, Jarrossay D, Facchetti F, et al. Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon. Nat Med. 1999;5:919–923
  20. Macatonia SE, Hosken NA, Litton M, et al. Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells. J Immunol. 1995;154:5071–5079
  21. Cella M, Scheidegger D, Palmer-Lehmann K, et al. Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. J Exp Med. 1996;184:747–752
  22. Reis e Sousa C, Hieny S, Scharton-Kersten T, et al. In vivo microbial stimulation induces rapid CD40 ligand-independent production of interleukin 12 by dendritic cells and their redistribution to T-cell areas. J Exp Med. 1997;186:1819–1829
  23. Pulendran B, Smith JL, Caspary G, et al. Distinct dendritic cell subsets differentially regulate the class of immune response in vivo. Proc Natl Acad Sci U S A. 1999;96:1036–1041
  24. Ito T, Amakawa R, Inaba M, et al. Differential regulation of human blood dendritic cell subsets by IFNs. J Immunol. 2001;166:2961–2969
  25. Monteleone I, Pallone F, Monteleone G. Interleukin-23 and Th17 cells in the control of gut inflammation. Mediators Inflamm. 2009;297645
  26. Bettelli E, Korn T, Oukka M, et al. Induction and effector functions of T(H)17 cells. Nature. 2008;453:1051–1057
  27. Sato T, Kanai T, Watanabe M, et al. Hyperexpression of inducible costimulator and its contribution on lamina propria T cells in inflammatory bowel disease. Gastroenterology. 2004;126:829–839
  28. Kamada N, Hisamatsu T, Okamoto S, et al. Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn's disease via IL-23/IFN-γ axis. J Clin Invest. 2008;118:2269–2280
  29. Szabo SJ, Kim ST, Costa GL, et al. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell. 2000;100:655–669
  30. Chakir H, Wang H, Lefebvre DE, et al. T-bet/GATA-3 ratio as a measure of the Th1/Th2 cytokine profile in mixed cell populations: predominant role of GATA-3. J Immunol Methods. 2003;278:157–169
  31. Stent G, Reece JC, Baylis DC, et al. Heterogeneity of freshly isolated human tonsil dendritic cells demonstrated by intracellular markers, phagocytosis, and membrane dye transfer. Cytometry. 2002;48:167–176
  32. Tsunoda R, Nakayama M, Onozaki K, et al. Isolation and long-term cultivation of human tonsil follicular dendritic cells. Virchows Arch. 1990;59:95–105
  33. Hart DN, McKenzie JL. Isolation and characterization of human tonsil dendritic cells. J Exp Med. 1988;168:157–170
  34. Bell SJ, Rigby R, English N, et al. Migration and maturation of human colonic dendritic cells. J Immunol. 2001;166:4958–4967
  35. McIlroy D, Troadec C, Grassi F, et al. Investigation of human spleen dendritic cell phenotype and distribution reveals evidence of in vivo activation in a subset of organ donors. Blood. 2001;97:3470–3477
  36. Depaolo RW, Tang F, Kim I, et al. Toll-like receptor 6 drives differentiation of tolerogenic dendritic cells and contributes to LcrV-mediated plague pathogenesis. Cell Host Microb. 2008;4:350–361
  37. Harrington LE, Hatton RD, Mangan PR, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6:1123–1132
  38. Pizarro TT, Michie MH, Bentz M, et al. IL-18, a novel immunoregulatory cytokine, is up-regulated in Crohn's disease: expression and localization in intestinal mucosal cells. J Immunol. 1999;162:6829–6835
  39. Sato T, Nakai T, Tamura N, et al. Osteopontin/Eta-1 up-regulated in Crohn's disease regulates the Th1 immune response. Gut. 2005;54:1254–1262
  40. Inoue N, Watanabe M, Sato T, et al. Restricted V(H) gene usage in lamina propria B cells producing anticolon antibody from patients with ulcerative colitis. Gastroenterology. 2001;121:15–23
  41. Fujino S, Andoh A, Bamba S, et al. Increased expression of interleukin 17 in inflammatory bowel disease. Gut. 2003;52:65–70
  42. Kleinschek MA, Boniface K, Sadekova S, et al. Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation. J Exp Med. 2009;206:525–534
  43. Assarsson N, Raf L. Incidence of granuloma in Crohn's disease. Acta Chir Scand. 1974;140:249–251
  44. Kamada N, Hisamatsu T, Okamoto S, et al. Abnormally differentiated subsets of intestinal macrophage play a key role in Th1-dominant chronic colitis through excess production of IL-12 and IL-23 in response to bacteria. J Immunol. 2005;175:6900–6908

 Conflicts of interest The authors disclose no conflicts.

 Funding Supported by the Japanese Ministry of Health, Labor and Welfare.

PII: S0016-5085(09)01248-7

doi: 10.1053/j.gastro.2009.07.049

Gastroenterology
Volume 137, Issue 5 , Pages 1736-1745 , November 2009

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