IL-17RD (Sef or IL-17RLM) interacts with IL-17 receptor and mediates IL-17 signaling

Cell Res. 2009 Feb;19(2):208-15. doi: 10.1038/cr.2008.320.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cell Line
  • Chlorocebus aethiops
  • Genes, Reporter
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin-17 / metabolism*
  • Signal Transduction

Substances

  • IL17RD protein, human
  • Interleukin-17
  • Receptors, Interleukin
  • Receptors, Interleukin-17