IL-27 regulates homeostasis of the intestinal CD4+ effector T cell pool and limits intestinal inflammation in a murine model of colitis

Journal of Immunology

Volumn 183, Issue 3, 2009, Pages 2037-2044

  Troy, Amy E ^a   Zaph, Colby ^a,c   Du, Yurong ^a   Taylor, Betsy C ^a   Guild, Katherine J ^a   Hunter, Christopher A ^a   Saris, Christiaan J M ^b   Artis, David ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b AMGEN INC   (United States)

^c UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

DEXTRAN SULFATE; GAMMA INTERFERON; INTERLEUKIN 17; INTERLEUKIN 27; IL27 PROTEIN, MOUSE; INTERLEUKIN DERIVATIVE; INTERLEUKIN RECEPTOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CD4+ T LYMPHOCYTE; CELL FUNCTION; CELLULAR IMMUNITY; COLITIS; COMPARATIVE STUDY; CONTROLLED STUDY; CYTOKINE PRODUCTION; DISEASE PREDISPOSITION; DISEASE SEVERITY; EFFECTOR CELL; HOMEOSTASIS AND REGULATION; INTESTINE CELL; LEUKOCYTE ACTIVATION; LYMPHOID TISSUE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; T LYMPHOCYTE SUBPOPULATION; TH1 CELL; TH17 CELL; WILD TYPE; ANIMAL; DISEASE MODEL; HELPER CELL; HOMEOSTASIS; IMMUNITY; IMMUNOLOGY; INFLAMMATION; INTESTINE; LYMPHOCYTE COUNT; PATHOLOGY; PHYSIOLOGY;

ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; COLITIS; DISEASE MODELS, ANIMAL; HOMEOSTASIS; IMMUNITY; INFLAMMATION; INTERLEUKIN-17; INTERLEUKINS; INTESTINES; LYMPHOCYTE COUNT; MICE; RECEPTORS, INTERLEUKIN; T-LYMPHOCYTES, HELPER-INDUCER;

EID: 68149163187     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.0802918     Document Type: Article

References (64)

1. + T helper cells. Cell 126: 1121-1133.
2. Zaph, C., Y. Du, S. A. Saenz, M. G. Nair, J. G. Perrigoue, B. C. Taylor, A. E. Troy, D. E. Kobuley, R. A. Kastelein, D. J. Cua, et al. 2008. Commensal-dependent expression of IL-25 regulates the IL-23-IL-17 axis in the intestine. J. Exp. Med. 205: 2191-2198.
3. + T helper-1 type responses to commensal bacteria in normal human intestinal lamina propria. Clin. Immunol. 131: 317-332.
4. Kleinschek, M. A., K. Boniface, S. Sadekova, J. Grein, E. E. Murphy, S. P. Turner, L. Raskin, B. Desai, W. A. Faubion, R. de Waal Malefyt, et al. 2009. Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation. J. Exp. Med. 206: 525-534.
5. Robinson, D. S., and A. O'Garra. 2002. Further checkpoints in Th1 development. Immunity 16: 755-758.
6. Happel, K. I., P. J. Dubin, M. Zheng, N. Ghilardi, C. Lockhart, L. J. Quinton, A. R. Odden, J. E. Shellito, G. J. Bagby, S. Nelson, and J. K. Kolls. 2005. Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae. J. Exp. Med. 202: 761-769.
7. Veldhoen, M., R. J. Hocking, C. J. Atkins, R. M. Locksley, and B. Stockinger. 2006. TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24: 179-189.
8. + T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nat. Immunol. 8: 369-377.
9. Stockinger, B., and M. Veldhoen. 2007. Differentiation and function of Th17 T cells. Curr. Opin. Immunol. 19: 281-286.
10. Lock, C., G. Hermans, R. Pedotti, A. Brendolan, E. Schadt, H. Garren, A. Langer-Gould, S. Strober, B. Cannella, J. Allard, et al. 2002. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat. Med. 8: 500-508.
11. Rangachari, M., N. Mauermann, R. R. Marty, S. Dirnhofer, M. O. Kurrer, V. Komnenovic, J. M. Penninger, and U. Eriksson. 2006. T-bet negatively regulates autoimmune myocarditis by suppressing local production of interleukin 17. J. Exp. Med. 203: 2009-2019.
12. Molet, S., Q. Hamid, F. Davoine, E. Nutku, R. Taha, N. Page, R. Olivenstein, J. Elias, and J. Chakir. 2001. IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J. Allergy Clin. Immunol. 108: 430-438. (Pubitemid 32881066)
13. Hwang, S. Y., and H. Y. Kim. 2005. Expression of IL-17 homologs and their receptors in the synovial cells of rheumatoid arthritis patients. Mol. Cells 19: 180-184.
14. + T cells. Immunity 1: 553-562.
15. Neurath, M. F., I. Fuss, B. L. Kelsall, E. Stuber, and W. Strober. 1995. Antibodies to interleukin 12 abrogate established experimental colitis in mice. J. Exp. Med. 182: 1281-1290.
16. Monteleone, I., P. Vavassori, L. Biancone, G. Monteleone, and F. Pallone. 2002. Immunoregulation in the gut: success and failures in human disease. Gut 50 Suppl 3: 60-64.
17. Yen, D., J. Cheung, H. Scheerens, F. Poulet, T. McClanahan, B. McKenzie, M. A. Kleinschek, A. Owyang, J. Mattson, W. Blumenschein, et al. 2006. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J. Clin. Invest. 116: 1310-1316.
18. Elson, C. O., Y. Cong, C. T. Weaver, T. R. Schoeb, T. K. McClanahan, R. B. Fick, and R. A. Kastelein. 2007. Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice. Gastroenterology 132: 2359-2370.
19. Uhlig, H. H., B. S. McKenzie, S. Hue, C. Thompson, B. Joyce-Shaikh, R. Stepankova, N. Robinson, S. Buonocore, H. Tlaskalova-Hogenova, D. J. Cua, and F. Powrie. 2006. Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity 25: 309-318.
20. Kullberg, M. C., D. Jankovic, C. G. Feng, S. Hue, P. L. Gorelick, B. S. McKenzie, D. J. Cua, F. Powrie, A. W. Cheever, K. J. Maloy, and A. Sher. 2006. IL-23 plays a key role in Helicobacter hepaticus-induced T cell-dependent colitis. J. Exp. Med. 203: 2485-2494.
21. Hue, S., P. Ahern, S. Buonocore, M. C. Kullberg, D. J. Cua, B. S. McKenzie, F. Powrie, and K. J. Maloy. 2006. Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J. Exp. Med. 203: 2473-2483.
22. Zhang, Z., M. Zheng, J. Bindas, P. Schwarzenberger, and J. K. Kolls. 2006. Critical role of IL-17 receptor signaling in acute TNBS-induced colitis. Inflamm. Bowel Dis. 12: 382-388.
23. Monteleone, G., L. Biancone, R. Marasco, G. Morrone, O. Marasco, F. Luzza, and F. Pallone. 1997. Interleukin 12 is expressed and actively released by Crohn's disease intestinal lamina propria mononuclear cells. Gastroenterology 112: 1169-1178.
24. Duerr, R. H., K. D. Taylor, S. R. Brant, J. D. Rioux, M. S. Silverberg, M. J. Daly, A. H. Steinhart, C. Abraham, M. Regueiro, A. Griffiths, et al. 2006. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314: 1461-1463.
25. Stumhofer, J. S., and C. A. Hunter. 2008. Advances in understanding the anti-inflammatory properties of IL-27. Immunol. Lett. 117: 123-130.
26. Yoshida, H., S. Hamano, G. Senaldi, T. Covey, R. Faggioni, S. Mu, M. Xia, A. C. Wakeham, H. Nishina, J. Potter, C. J. Saris, and T. W. Mak. 2001. WSX-1 is required for the initiation of Th1 responses and resistance to L. major infection. Immunity 15: 569-578.
27. + T cells. Immunity 16: 779-790.
28. Pflanz, S., L. Hibbert, J. Mattson, R. Rosales, E. Vaisberg, J. F. Bazan, J. H. Phillips, T. K. McClanahan, R. de Waal Malefyt, and R. A. Kastelein. 2004. WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27. J. Immunol. 172: 2225-2231.
29. Kastelein, R. A., C. A. Hunter, and D. J. Cua. 2007. Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annu. Rev. Immunol. 25: 221-242.
30. Villarino, A. V., J. Larkin, 3rd, C. J. Saris, A. J. Caton, S. Lucas, T. Wong, F. J. de Sauvage, and C. A. Hunter. 2005. Positive and negative regulation of the IL-27 receptor during lymphoid cell activation. J. Immunol. 174: 7684-7691. (Pubitemid 40806273)
31. Holscher, C., A. Holscher, D. Ruckerl, T. Yoshimoto, H. Yoshida, T. Mak, C. Saris, and S. Ehlers. 2005. The IL-27 receptor chain WSX-1 differentially regulates antibacterial immunity and survival during experimental tuberculosis. J. Immunol. 174: 3534-3544. (Pubitemid 40354062)
32. Wirtz, S., I. Tubbe, P. R. Galle, H. J. Schild, M. Birkenbach, R. S. Blumberg, and M. F. Neurath. 2006. Protection from lethal septic peritonitis by neutralizing the biological function of interleukin 27. J. Exp. Med. 203: 1875-1881.
33. Takeda, A., S. Hamano, A. Yamanaka, T. Hanada, T. Ishibashi, T. W. Mak, A. Yoshimura, and H. Yoshida. 2003. Cutting edge: role of IL-27/WSX-1 signaling for induction of T-bet through activation of STAT1 during initial Th1 commitment. J. Immunol. 170: 4886-4890.
34. Artis, D., A. Villarino, M. Silverman, W. He, E. M. Thornton, S. Mu, S. Summer, T. M. Covey, E. Huang, H. Yoshida, et al. 2004. The IL-27 receptor (WSX-1) is an inhibitor of innate and adaptive elements of type 2 immunity. J. Immunol. 173: 5626-5634.
35. Villarino, A., L. Hibbert, L. Lieberman, E. Wilson, T. Mak, H. Yoshida, R. A. Kastelein, C. Saris, and C. A. Hunter. 2003. The IL-27R (WSX-1) is required to suppress T cell hyperactivity during infection. Immunity 19: 645-655.
36. Hunter, C. A. 2005. New IL-12-family members: IL-23 and IL-27, cytokines with divergent functions. Nat. Rev. Immunol. 5: 521-531.
37. Stumhofer, J. S., A. Laurence, E. H. Wilson, E. Huang, C. M. Tato, L. M. Johnson, A. V. Villarino, Q. Huang, A. Yoshimura, D. Sehy, et al. 2006. Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat. Immunol. 7: 937-945.
38. Batten, M., J. Li, S. Yi, N. M. Kljavin, D. M. Danilenko, S. Lucas, J. Lee, F. J. de Sauvage, and N. Ghilardi. 2006. Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells. Nat. Immunol. 7: 929-936.
39. Cua, D. J., and R. A. Kastelein. 2006. TGF-β, a 'double agent' in the immune pathology war. Nat. Immunol. 7: 557-559.
40. Kalliolias, G. D., and L. B. Ivashkiv. 2008. IL-27 activates human monocytes via STAT1 and suppresses IL-10 production but the inflammatory functions of IL-27 are abrogated by TLRs and p38. J. Immunol. 180: 6325-6333.
41. Zaph, C., A. E. Troy, B. C. Taylor, L. D. Berman-Booty, K. J. Guild, Y. Du, E. A. Yost, A. D. Gruber, M. J. May, F. R. Greten, et al. 2007. Epithelial-cell-intrinsic IKK-β expression regulates intestinal immune homeostasis. Nature 446: 552-556.
42. Sutton, C., C. Brereton, B. Keogh, K. H. Mills, and E. C. Lavelle. 2006. A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis. J. Exp. Med. 203: 1685-1691.
43. Byrne, F. R., and J. L. Viney. 2006. Mouse models of inflammatory bowel disease. Curr. Opin. Drug Discov. Devel. 9: 207-217.
44. Kim, T. W., J. N. Seo, Y. H. Suh, H. J. Park, J. H. Kim, J. Y. Kim, and K. I. Oh. 2006. Involvement of lymphocytes in dextran sulfate sodium-induced experimental colitis. World J. Gastroenterol. 12: 302-305.
45. Fiorentino, D. F., A. Zlotnik, T. R. Mosmann, M. Howard, and A. O'Garra. 1991. IL-10 inhibits cytokine production by activated macrophages. J. Immunol. 147: 3815-3822.
46. + T cells partially through STAT3-dependent mechanism. J. Immunol. 177: 5377-5385.
47. + T cells through Stat1-dependent and -independent mechanisms. Proc. Natl. Acad. Sci. USA 100: 15047-15052.
48. + effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat. Immunol. 6: 1123-1132.
49. Park, H., Z. Li, X. O. Yang, S. H. Chang, R. Nurieva, Y. H. Wang, Y. Wang, L. Hood, Z. Zhu, Q. Tian, and C. Dong. 2005. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat. Immunol. 6: 1133-1141.
50. Schreiber, S., P. Rosenstiel, J. Hampe, S. Nikolaus, B. Groessner, A. Schottelius, T. Kuhbacher, J. Hamling, U. R. Folsch, and D. Seegert. 2002. Activation of signal transducer and activator of transcription (STAT) 1 in human chronic inflammatory bowel disease. Gut 51: 379-385.
51. Wu, F., T. Dassopoulos, L. Cope, A. Maitra, S. R. Brant, M. L. Harris, T. M. Bayless, G. Parmigiani, and S. Chakravarti. 2007. Genome-wide gene expression differences in Crohn's disease and ulcerative colitis from endoscopic pinch biopsies: insights into distinctive pathogenesis. Inflamm. Bowel Dis. 13: 807-821.
52. Suzuki, A., T. Hanada, K. Mitsuyama, T. Yoshida, S. Kamizono, T. Hoshino, M. Kubo, A. Yamashita, M. Okabe, K. Takeda, et al. 2001. CIS3/SOCS3/SSI3 plays a negative regulatory role in STAT3 activation and intestinal inflammation. J. Exp. Med. 193: 471-481.
53. Mazmanian, S. K., C. H. Liu, A. O. Tzianabos, and D. L. Kasper. 2005. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122: 107-118.
54. Ivanov, I. I., L. Frutos Rde, N. Manel, K. Yoshinaga, D. B. Rifkin, R. B. Sartor, B. B. Finlay, and D. R. Littman. 2008. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbes 4: 337-349.
55. Nieuwenhuis, E. E., M. F. Neurath, N. Corazza, H. Iijima, J. Trgovcich, S. Wirtz, J. Glickman, D. Bailey, M. Yoshida, P. R. Galle, et al. 2002. Disruption of T helper 2-immune responses in Epstein-Barr virus-induced gene 3-deficient mice. Proc. Natl. Acad. Sci. USA 99: 16951-16956.
56. Villarino, A. V., D. Artis, J. S. Bezbradica, O. Miller, C. J. Saris, S. Joyce, and C. A. Hunter. 2008. IL-27R deficiency delays the onset of colitis and protects from helminth-induced pathology in a model of chronic IBD. Int. Immunol. 20: 739-752.
57. Honda, K., K. Nakamura, N. Matsui, M. Takahashi, Y. Kitamura, T. Mizutani, N. Harada, H. Nawata, S. Hamano, and H. Yoshida. 2005. T helper 1-inducing property of IL-27/WSX-1 signaling is required for the induction of experimental colitis. Inflamm. Bowel Dis. 11: 1044-1052.
58. Ogawa, A., A. Andoh, Y. Araki, T. Bamba, and Y. Fujiyama. 2004. Neutralization of interleukin-17 aggravates dextran sulfate sodium-induced colitis in mice. Clin. Immunol. 110: 55-62.
59. Kinugasa, T., T. Sakaguchi, X. Gu, and H. C. Reinecker. 2000. Claudins regulate the intestinal barrier in response to immune mediators. Gastroenterology 118: 1001-1011. (Pubitemid 30346975)
60. Rakoff-Nahoum, S., L. Hao, and R. Medzhitov. 2006. Role of toll-like receptors in spontaneous commensal-dependent colitis. Immunity 25: 319-329.
61. Takatori, H., Y. Kanno, W. T. Watford, C. M. Tato, G. Weiss, Ivanov, II, D. R. Littman, and J. J. O'Shea. 2009. Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22. J. Exp. Med. 206: 35-41.
62. Reindl, W., S. Weiss, H. A. Lehr, and I. Forster. 2007. Essential crosstalk between myeloid and lymphoid cells for development of chronic colitis in myeloid-specific signal transducer and activator of transcription 3-deficient mice. Immunology 120: 19-27.
63. Tlaskalova-Hogenova, H., L. Tuckova, R. Stepankova, T. Hudcovic, L. Palova-Jelinkova, H. Kozakova, P. Rossmann, D. Sanchez, J. Cinova, T. Hrncir, et al. 2005. Involvement of innate immunity in the development of inflammatory and autoimmune diseases. Ann. NY Acad. Sci. 1051: 787-798.
64. McGovern, D., and F. Powrie. 2007. The IL23 axis plays a key role in the pathogenesis of IBD. Gut 56: 1333-1336.