Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F

J Immunol. 2007 Oct 15;179(8):5462-73. doi: 10.4049/jimmunol.179.8.5462.

Rolf E Kuestner ¹, David W Taft, Aaron Haran, Cameron S Brandt, Ty Brender, Karen Lum, Brandon Harder, Shannon Okada, Craig D Ostrander, James L Kreindler, Shean J Aujla, Brian Reardon, Margaret Moore, Pamela Shea, Randall Schreckhise, Thomas R Bukowski, Scott Presnell, Patricia Guerra-Lewis, Julia Parrish-Novak, Jeff L Ellsworth, Stephen Jaspers, Katherine E Lewis, Mark Appleby, Jay K Kolls, Mark Rixon, James W West, Zeren Gao, Steven D Levin

Affiliations

Affiliation

1 Department of Molecular and Cell Based Discovery, ZymoGenetics Incroporated, Seattle, WA 98102, USA.

PMID: 17911633 DOI: 10.4049/jimmunol.179.8.5462

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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