title: The IL-27 receptor (WSX-1) is an inhibitor of innate and adaptive elements of type 2 immunity.
abstract: Although previous studies have investigated the role of IL-27/WSX-1 interactions in the regulation of Th1 responses, little is known about their role in regulating Th2-type responses. Studies presented in this work identify a direct role for IL-27/WSX-1 interactions in the negative regulation of type 2 responses independent of effects on type 1 cytokines. WSX-1-/- mice infected with the gastrointestinal helminth Trichuris muris displayed accelerated expulsion of parasites and the development of exaggerated goblet cell hyperplasia and mastocytosis in the gut due to increased production of Th2 cytokines. Enhanced mast cell activity in the absence of WSX-1 was consistent with the ability of wild-type mast cells to express this receptor. In addition, IL-27 directly suppressed CD4+ T cell proliferation and Th2 cytokine production. Together, these studies identify a novel role for IL-27/WSX-1 in limiting innate and adaptive components of type 2 immunity at mucosal sites.
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: David
authors.initials: D
authors.lastname: Artis
authors.forename: Alejandro
authors.initials: A
authors.lastname: Villarino
authors.forename: Michael
authors.initials: M
authors.lastname: Silverman
authors.forename: Weimian
authors.initials: W
authors.lastname: He
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Thornton
authors.forename: Sharon
authors.initials: S
authors.lastname: Mu
authors.forename: Shamin
authors.initials: S
authors.lastname: Summer
authors.forename: Todd M
authors.initials: TM
authors.lastname: Covey
authors.forename: Elaine
authors.initials: E
authors.lastname: Huang
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yoshida
authors.forename: Gary
authors.initials: G
authors.lastname: Koretzky
authors.forename: Michael
authors.initials: M
authors.lastname: Goldschmidt
authors.forename: Gary D
authors.initials: GD
authors.lastname: Wu
authors.forename: Fred
authors.initials: F
authors.lastname: de Sauvage
authors.forename: Hugh R P
authors.initials: HR
authors.lastname: Miller
authors.forename: Christiaan J M
authors.initials: CJ
authors.lastname: Saris
authors.forename: Phillip
authors.initials: P
authors.lastname: Scott
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hunter
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000276:immunology*; D020397:Goblet Cells / Q000276:immunology / Q000473:pathology; D007113:Immunity, Innate / Q000235:genetics; D018928:Immunity, Mucosal / Q000235:genetics; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007411:Intestinal Diseases, Parasitic / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008415:Mastocytosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D018121:Receptors, Cytokine / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018123:Receptors, Interleukin; D013491:Suppressor Factors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D014257:Trichuriasis / Q000235:genetics / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D014258:Trichuris / Q000254:growth & development / Q000276:immunology
chemical_list: D016207:Cytokines; C486767:Il27 protein, mouse; C484747:Il27ra protein, mouse; D007378:Interleukins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D013491:Suppressor Factors, Immunologic; D007371:Interferon-gamma