IL-17RC Is Required for IL-17A-and IL-17F-Dependent Signaling and the Pathogenesis of Experimental Autoimmune Encephalomyelitis

被引：120

作者：

Hu, Yan ^{[1
]}

Ota, Naruhisa ^{[1
]}

Peng, Ivan ^{[1
]}

Refino, Canio J. ^{[1
]}

Danilenko, Dimitry M. ^{[2
]}

Caplazi, Patrick ^{[2
]}

Ouyang, Wenjun ^{[1
]}

机构：

[1] Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA

[2] Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA

来源：

JOURNAL OF IMMUNOLOGY | 2010年 / 184卷 / 08期

关键词：

COLLAGEN-INDUCED ARTHRITIS; COLONY-STIMULATING FACTOR; INTERLEUKIN-17; RECEPTOR; HOST-DEFENSE; T-CELL; CUTTING EDGE; HETERODIMERIC CYTOKINE; NEUTROPHIL RECRUITMENT; CARTILAGE DESTRUCTION; RHEUMATOID-ARTHRITIS;

D O I：

10.4049/jimmunol.0903614

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

It has been suggested that IL-17RC forms a complex with IL-17RA to mediate the functions of IL-17A and IL-17F homodimers as well as IL-17A/F heterodimers. It is still unclear whether IL-17RC is absolutely required for the signaling of IL-17 cytokines in vivo. By using Il-17rc-deficient mice, we show that IL-17RC is essential for the signaling of IL-17A, IL-17F, and IL-17A/F both in vitro and in vivo. IL-17RC does not preassociate with IL-17RA on the cell surface; rather IL-17A can induce the formation of an IL-17RC and IL-17RA complex. This process is not dependent on the intracellular similar expression to fibroblast growth factor genes and IL-17Rs (SEFIR) domain of IL-17RC, but the SEFIR is essential in IL-17A signal transduction. Finally, Il-17rc(-/-) mice develop much milder disease in an experimental autoimmune encephalomyelitis model, supporting an essential role for IL-17RC in mediating immune-mediated CNS inflammation. The Journal of Immunology, 2010, 184: 4307-4316.

引用

页码：4307 / 4316

页数：10

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