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The Journal of Immunology, 2006, 177: 36-39.
Copyright © 2006 by The American Association of Immunologists


CUTTING EDGE

Cutting Edge: Interleukin 17 Signals through a Heteromeric Receptor Complex

Dean Toy*, David Kugler*, Martin Wolfson{dagger}, Tim Vanden Bos{dagger}, Jesse Gurgel{ddagger}, Jonathan Derry§, Joel Tocker* and Jacques Peschon1,*

Departments of * Inflammation, {dagger} Protein Sciences, {ddagger} Oncology, and § Molecular Sciences, Amgen, Seattle WA 98119

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.




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