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  • Identification of the IL-17...
    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

    Journal of Immunology, 10/2007, Letnik: 179, Številka: 8
    Journal Article

    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.