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
  • 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.