A crucial role for interleukin (IL)-1 in the induction of IL-17–producing T cells that mediate autoimmune encephalomyelitis

Journal of Experimental Medicine - Tập 203 Số 7 - Trang 1685-1691 - 2006
Caroline E. Sutton1, Corinna F. Brereton2, Brian Keogh2, Kingston H. G. Mills2, Ed C. Lavelle3
1Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland
21Immune Regulation Research Group
32Adjuvant Research Group, School of Biochemistry and Immunology, Trinity College, Dublin 2, Irel

Tóm tắt

It was recently demonstrated that interleukin (IL)-23–driven IL-17–producing (ThIL-17) T cells mediate inflammatory pathology in certain autoimmune diseases. We show that the induction of antigen-specific ThIL-17 cells, but not T helper (Th)1 or Th2 cells, by immunization with antigens and adjuvants is abrogated in IL-1 receptor type I–deficient (IL-1RI−/−) mice. Furthermore, the incidence of experimental autoimmune encephalomyelitis (EAE) was significantly lower in IL-1RI−/− compared with wild-type mice, and this correlated with a failure to induce autoantigen-specific ThIL-17 cells, whereas induction of Th1 and Th2 responses was not substantially different. However, EAE was induced in IL-1RI−/− mice by adoptive transfer of autoantigen-specific cells from wild-type mice with EAE. IL-23 alone did not induce IL-17 production by T cells from IL-1RI−/− mice, and IL-23–induced IL-17 production was substantially enhanced by IL-1α or IL-1β, even in the absence of T cell receptor stimulation. We demonstrate essential roles for phosphatidylinositol 3-kinase, nuclear factor κB, and novel protein kinase C isoforms in IL-1– and IL-23–mediated IL-17 production. Tumor necrosis factor α also synergized with IL-23 to enhance IL-17 production, and this was IL-1 dependent. Our findings demonstrate that IL-1 functions upstream of IL-17 to promote pathogenic ThIL-17 cells in EAE.

Từ khóa


Tài liệu tham khảo

2001, Nat. Immunol., 2, 762, 10.1038/ni0901-762

2006, Trends Immunol., 27, 17, 10.1016/j.it.2005.10.003

1996, Eur. J. Immunol., 26, 1641, 10.1002/eji.1830260735

2003, Nature., 421, 744, 10.1038/nature01355

2003, J. Biol. Chem., 278, 1910, 10.1074/jbc.M207577200

2005, J. Exp. Med., 201, 233, 10.1084/jem.20041257

2003, J. Exp. Med., 198, 1951, 10.1084/jem.20030896

2005, Nat. Immunol., 6, 1123, 10.1038/ni1254

2005, Nat. Immunol., 6, 1133, 10.1038/ni1261

2005, Arthritis Rheum., 52, 3239, 10.1002/art.21342

2005, Am. J. Pathol., 167, 141, 10.1016/S0002-9440(10)62961-6

2000, Clin. Immunol., 95, 117, 10.1006/clim.2000.4851

2002, J. Neuroimmunol., 126, 172, 10.1016/S0165-5728(02)00056-5

2006, Int. Immunol., 18, 399, 10.1093/intimm/dxh379

2005, Cell. Immunol., 237, 123, 10.1016/j.cellimm.2005.11.002

2005, Annu. Rev. Immunol., 23, 683, 10.1146/annurev.immunol.23.021704.115707

2006, Immunity., 24, 179, 10.1016/j.immuni.2006.01.001

2006, Nature., 441, 231, 10.1038/nature04754

2006, Nature., 441, 235, 10.1038/nature04753

2006, J. Immunol., 176, 2872, 10.4049/jimmunol.176.5.2872

2001, J. Immunol., 166, 5665, 10.4049/jimmunol.166.9.5665

2005, Arthritis Res. Ther., 7, R139, 10.1186/ar1470

2004, J. Biol. Chem., 279, 52762, 10.1074/jbc.M405764200

2004, J. Clin. Invest., 114, 1603, 10.1172/JCI20742

2003, Proc. Natl. Acad. Sci. USA., 100, 5986, 10.1073/pnas.1035999100

2005, J. Clin. Invest., 115, 282, 10.1172/JCI200523394

2005, J. Immunol., 175, 2721, 10.4049/jimmunol.175.4.2721

2004, J. Biol. Chem., 279, 2559, 10.1074/jbc.M308809200

Thông tin
Thông tin xuất bản

Journal of Experimental Medicine

Tập 203 Số 7

1685-1691

Thông tin tác giả