Cutting edge: interleukin 17 signals through a heteromeric receptor complex

J Immunol. 2006 Jul 1;177(1):36-9. doi: 10.4049/jimmunol.177.1.36.


IL-17 is an inflammatory cytokine produced primarily by a unique lineage of CD4 T cells that plays critical roles in the pathogenesis of multiple autoimmune diseases. IL-17RA is a ubiquitously expressed receptor that is essential for IL-17 biologic activity. Despite widespread receptor expression, the activity of IL-17 is most classically defined by its ability to induce the expression of inflammatory cytokines, chemokines, and other mediators by stromal cells. The lack of IL-17 responsiveness in mouse stromal cells genetically deficient in IL-17RA is poorly complemented by human IL-17RA, suggesting the presence of an obligate ancillary component whose activity is species specific. This component is IL-17RC, a distinct member of the IL-17R family. Thus, the biologic activity of IL-17 is dependent on a complex composed of IL-17RA and IL-17RC, suggesting a new paradigm for understanding the interactions between the expanded family of IL-17 ligands and their receptors.

MeSH terms

  • Animals
  • Cell Line
  • Cell Line, Transformed
  • Fibroblasts / immunology
  • Fibroblasts / metabolism
  • Humans
  • Interleukin-17 / metabolism
  • Interleukin-17 / physiology*
  • Ligands
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Subunits / chemistry
  • Protein Subunits / physiology
  • Receptors, Interleukin / chemistry*
  • Receptors, Interleukin / deficiency
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin / physiology*
  • Receptors, Interleukin-17
  • Signal Transduction / immunology*


  • IL17RA protein, human
  • Il17ra protein, mouse
  • Il17rb protein, mouse
  • Il17rc protein, mouse
  • Il17rd protein, mouse
  • Interleukin-17
  • Ligands
  • Protein Subunits
  • Receptors, Interleukin
  • Receptors, Interleukin-17