IL-17RC is required for IL-17A- and IL-17F-dependent signaling and the pathogenesis of experimental autoimmune encephalomyelitis.
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.
Hu
Yan
Y
Department of Immunology, Genentech, South San Francisco, CA 94080, USA.
Ota
Naruhisa
N
Peng
Ivan
I
Refino
Canio J
CJ
Danilenko
Dimitry M
DM
Caplazi
Patrick
P
Ouyang
Wenjun
W
D000818:Animals; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D018920:Coculture Techniques; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020381:Interleukin-17 / Q000502:physiology*; D007378:Interleukins / Q000502:physiology; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*
C098680:Il17a protein, mouse; C515932:Il17f protein, mouse; C508527:Il17rc protein, mouse; D020381:Interleukin-17; D007378:Interleukins; C442281:Mydgf protein, mouse; D018123:Receptors, Interleukin