Cutting edge: interleukin 17 signals through a heteromeric receptor complex.
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.
Toy
Dean
D
Department of Inflammation, Amgen, 1201 Amgen Court West, Seattle, WA 98119, USA.
Kugler
David
D
Wolfson
Martin
M
Vanden Bos
Tim
T
Gurgel
Jesse
J
Derry
Jonathan
J
Tocker
Joel
J
Peschon
Jacques
J
D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism / Q000502:physiology*; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D021122:Protein Subunits / Q000737:chemistry / Q000502:physiology; D018123:Receptors, Interleukin / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053722:Receptors, Interleukin-17; D015398:Signal Transduction / Q000276:immunology*
C109985:IL17RA protein, human; C491673:Il17ra protein, mouse; C485810:Il17rb protein, mouse; C508527:Il17rc protein, mouse; C508528:Il17rd protein, mouse; D020381:Interleukin-17; D008024:Ligands; D021122:Protein Subunits; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17