Journal
CELL RESEARCH
Volume 19, Issue 2, Pages 208-215Publisher
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/cr.2008.320
Keywords
IL-17RD; sef; IL-17; IL-17R; IL-17 signaling; heteromeric receptor complex; T(H)17
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Funding
- Tsinghua-Yu-Yuan Medical Sciences Fund
- National Natural Science Foundation of China [30530420, 30470888, 30518002]
- Chinese National Support Project [2006CB910102, 2002CB513007]
- China-Canada Joint Health Research [CCI-82411, 30611120522]
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Interleukin-17 (IL-17 or IL-17A) production is a hallmark of T(H)17 cells, a new unique lineage of CD4(+) T lymphocytes contributing to the pathogenesis of multiple autoimmune and inflammatory diseases. IL-17 receptor (IL-17R or IL-17RA) is essential for IL-17 biological activity. Emerging data suggest that the formation of a heteromeric and/or homomeric receptor complex is required for IL-17 signaling. Here we show that the orphan receptor IL-17RD (Sef, similar expression to FGF genes or IL-17RLM) is associated and colocalized with IL-17R. Importantly, IL-17RD mediates IL-17 signaling, as evaluated using a luciferase reporter driven by the native promoter of 24p3, an IL-17 target gene. In addition, an IL-17RD mutant lacking the intracellular domain dominant-negatively suppresses IL-17R-mediated IL-17 signaling. Moreover, IL-17RD as well as IL-17R is associated with TRAF6, an IL-17R downstream molecule. These results indicate that IL-17RD is a part of the IL- 17 receptor signaling complex, therefore providing novel evidence for IL- 17 signaling through a heteromeric and/or homomeric receptor complex.
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