Rong Zhili, Wang Anan, Li Zhiyong, Ren Yongming, Cheng Long, Li Yinghua, Wang Yinyin, Ren Fangli, Zhang Xiaoning, Hu Jim, Chang Zhijie
School of Medicine, Department of Biological Sciences and Biotechnology, State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China.
Cell Res. 2009 Feb;19(2):208-15. doi: 10.1038/cr.2008.320.
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.
白细胞介素-17（IL-17或IL-17A）的产生是辅助性T细胞17（T(H)17细胞）的一个标志，T(H)17细胞是CD4(+) T淋巴细胞的一个新的独特谱系，参与多种自身免疫性疾病和炎症性疾病的发病机制。白细胞介素-17受体（IL-17R或IL-17RA）对于IL-17的生物学活性至关重要。新出现的数据表明，IL-17信号传导需要形成异源和/或同源受体复合物。在此，我们表明孤儿受体IL-17RD（Sef，与FGF基因或IL-17RLM表达相似）与IL-17R相关并共定位。重要的是，使用由IL-17靶基因24p3的天然启动子驱动的荧光素酶报告基因评估发现，IL-17RD介导IL-17信号传导。此外，缺乏细胞内结构域的IL-17RD突变体以显性负性方式抑制IL-17R介导的IL-17信号传导。而且，IL-17RD以及IL-17R与IL-17R下游分子TRAF6相关。这些结果表明，IL-17RD是IL-17受体信号复合物的一部分，因此为通过异源和/或同源受体复合物进行的IL-17信号传导提供了新的证据。
