A crucial role for IL-1 in the induction of IL-17 producing T cells that mediate autoimmune encephalomyelitis
Citation:
Sutton, C., Brereton, C., Keogh, B., Mills, K.H.G. Lavelle, E.C. `A crucial role for IL-1 in the induction of IL-17 producing T cells that mediate autoimmune encephalomyelitis? in The Journal of Experimental Medicine, 203, (7), 2006, pp 1685 - 1691Download Item:
A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis.pdf (published (publisher copy) peer-reviewed) 1.105Mb
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-1? or IL-1?, even in the absence of T cell receptor stimulation. We demonstrate essential roles for phosphatidylinositol 3-kinase, nuclear factor ?B, and novel protein kinase C isoforms in IL-1? and IL-23?mediated IL-17 production. Tumor necrosis factor ? 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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Grant Number
Science Foundation Ireland
Author's Homepage:
http://people.tcd.ie/lavelleeDescription:
PUBLISHED
Author: LAVELLE, EDWARD; MILLS, KINGSTON
Publisher:
The Rockefeller University PressType of material:
Journal ArticleCollections:
Series/Report no:
The Journal of Experimental Medicine203
7
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BiochemistryISSN:
http://dx.doi.org/10.1084/jem.20060285Licences: