期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 45, 期 5, 页码 1339-1347出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201445064
关键词
Autoantibodies; B-cell tolerance; Experimental autoimmune myasthenia gravis; IL-17; IgG subtypes; Th17 cells
类别
资金
- DFG [SFB 650, EXC 257]
- BMBF
- Netherlands Organization for Scientific Research [916.10.148]
- Brain Foundation of the Netherlands [FS2008(1)-28]
The role of Th17 cells in the pathogenesis of autoantibody-mediated diseases is unclear. Here, we assessed the contribution of Th17 cells to the pathogenesis of experimental autoimmune myasthenia gravis (EAMG), which is induced by repetitive immunizations with Torpedo californica acetylcholine receptor (tAChR). We show that a significant fraction of tAChR-specific CD4(+) T cells is producing IL-17. IL-17(ko) mice developed fewer or no EAMG symptoms, although the frequencies of tAChR-specific CD4(+) T cells secreting IL-2, IFN-, or IL-21, and the percentage of FoxP3(+) T-reg cells were similar to WT mice. Even though the total anti-tAChR antibody levels were equal, the complement fixating IgG2b subtype was reduced in IL-17(ko) as compared to WT mice. Most importantly, pathogenic anti-murine AChR antibodies were significantly lower in IL-17(ko) mice. Furthermore, we confirmed the role of Th17 cells in EAMG pathogenesis by the reconstitution of TCR /(ko) mice with WT or IL-17(ko) CD4(+) T cells. In conclusion, we show that the level of IgG2b and the loss of B-cell tolerance, which results in pathogenic anti-murine AChR-specific antibodies, are dependent on IL-17 production by CD4(+) T cells. Thus, we describe here for the first time how Th17 cells are involved in the induction of classical antibody-mediated autoimmunity.
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