IL-17RD (Sef or IL-17RLM) interacts with IL-17 receptor and mediates IL-17 signaling.
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.
Rong
Zhili
Z
School of Medicine, Department of Biological Sciences and Biotechnology, State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China.
Wang
Anan
A
Li
Zhiyong
Z
Ren
Yongming
Y
Cheng
Long
L
Li
Yinghua
Y
Wang
Yinyin
Y
Ren
Fangli
F
Zhang
Xiaoning
X
Hu
Jim
J
Chang
Zhijie
Z
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D017930:Genes, Reporter; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism*; D053722:Receptors, Interleukin-17 / Q000378:metabolism*; D015398:Signal Transduction
C477526:IL17RD protein, human; D020381:Interleukin-17; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17