title: Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F.
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.
authors.affiliation: Department of Molecular and Cell Based Discovery, ZymoGenetics Incroporated, Seattle, WA 98102, USA.
authors.forename: Rolf E
authors.initials: RE
authors.lastname: Kuestner
authors.forename: David W
authors.initials: DW
authors.lastname: Taft
authors.forename: Aaron
authors.initials: A
authors.lastname: Haran
authors.forename: Cameron S
authors.initials: CS
authors.lastname: Brandt
authors.forename: Ty
authors.initials: T
authors.lastname: Brender
authors.forename: Karen
authors.initials: K
authors.lastname: Lum
authors.forename: Brandon
authors.initials: B
authors.lastname: Harder
authors.forename: Shannon
authors.initials: S
authors.lastname: Okada
authors.forename: Craig D
authors.initials: CD
authors.lastname: Ostrander
authors.forename: James L
authors.initials: JL
authors.lastname: Kreindler
authors.forename: Shean J
authors.initials: SJ
authors.lastname: Aujla
authors.forename: Brian
authors.initials: B
authors.lastname: Reardon
authors.forename: Margaret
authors.initials: M
authors.lastname: Moore
authors.forename: Pamela
authors.initials: P
authors.lastname: Shea
authors.forename: Randall
authors.initials: R
authors.lastname: Schreckhise
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Bukowski
authors.forename: Scott
authors.initials: S
authors.lastname: Presnell
authors.forename: Patricia
authors.initials: P
authors.lastname: Guerra-Lewis
authors.forename: Julia
authors.initials: J
authors.lastname: Parrish-Novak
authors.forename: Jeff L
authors.initials: JL
authors.lastname: Ellsworth
authors.forename: Stephen
authors.initials: S
authors.lastname: Jaspers
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Lewis
authors.forename: Mark
authors.initials: M
authors.lastname: Appleby
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
authors.forename: Mark
authors.initials: M
authors.lastname: Rixon
authors.forename: James W
authors.initials: JW
authors.lastname: West
authors.forename: Zeren
authors.initials: Z
authors.lastname: Gao
authors.forename: Steven D
authors.initials: SD
authors.lastname: Levin
mesh_terms: D017398:Alternative Splicing / Q000276:immunology; D000818:Animals; D001667:Binding, Competitive / Q000276:immunology; D002460:Cell Line; D006224:Cricetinae; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism / Q000627:therapeutic use; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D013045:Species Specificity; D014162:Transfection
chemical_list: D018836:Inflammation Mediators; D020381:Interleukin-17; D053722:Receptors, Interleukin-17