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

Caroline Sutton; Corinna Brereton; Brian Keogh; Kingston H.G. Mills; Ed C. Lavelle

doi:10.1084/jem.20060285

journal article Jul 03, 2006

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

Caroline Sutton Corinna Brereton Brian Keogh Kingston H.G. Mills Ed C. Lavelle

The Journal of Experimental Medicine Vol. 203 No. 7 pp. 1685-1691 · Rockefeller University Press

View at Publisher Save 10.1084/jem.20060285

Abstract

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.

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Details

Published: Jul 03, 2006
Vol/Issue: 203(7)
Pages: 1685-1691

Authors

C

Caroline Sutton

1Immune Regulation Research Group

C

Corinna Brereton

1Immune Regulation Research Group

B

Brian Keogh

1Immune Regulation Research Group

K

Kingston H.G. Mills

1Immune Regulation Research Group

E

Ed C. Lavelle

2Adjuvant Research Group, School of Biochemistry and Immunology, Trinity College, Dublin 2, Irel

Cite This Article

Caroline Sutton, Corinna Brereton, Brian Keogh, et al. (2006). A crucial role for interleukin (IL)-1 in the induction of IL-17–producing T cells that mediate autoimmune encephalomyelitis. The Journal of Experimental Medicine, 203(7), 1685-1691. https://doi.org/10.1084/jem.20060285

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

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