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Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F
Authors:Kuestner Rolf E  Taft David W  Haran Aaron  Brandt Cameron S  Brender Ty  Lum Karen  Harder Brandon  Okada Shannon  Ostrander Craig D  Kreindler James L  Aujla Shean J  Reardon Brian  Moore Margaret  Shea Pamela  Schreckhise Randall  Bukowski Thomas R  Presnell Scott  Guerra-Lewis Patricia  Parrish-Novak Julia  Ellsworth Jeff L  Jaspers Stephen  Lewis Katherine E  Appleby Mark  Kolls Jay K  Rixon Mark  West James W  Gao Zeren  Levin Steven D
Institution:Department of Molecular and Cell Based Discovery, ZymoGenetics Incroporated, Seattle, WA 98102, USA.
Abstract:The proinflammatory cytokines IL-17A and IL-17F have a high degree of sequence similarity and share many biological properties. Both have been implicated as factors contributing to the progression of inflammatory and autoimmune diseases. Moreover, reagents that neutralize IL-17A significantly ameliorate disease severity in several mouse models of human disease. IL-17A mediates its effects through interaction with its cognate receptor, the IL-17 receptor (IL-17RA). We report here that the IL-17RA-related molecule, IL-17RC is the receptor for IL-17F. Notably, both IL-17A and IL-17F bind to IL-17RC with high affinity, leading us to suggest that a soluble form of this molecule may serve as an effective therapeutic antagonist of IL-17A and IL-17F. We generated a soluble form of IL-17RC and demonstrate that it effectively blocks binding of both IL-17A and IL-17F, and that it inhibits signaling in response to these cytokines. Collectively, our work indicates that IL-17RC functions as a receptor for both IL-17A and IL-17F and that a soluble version of this protein should be an effective antagonist of IL-17A and IL-17F mediated inflammatory diseases.
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