The IL-27 receptor (WSX-1) is an inhibitor of innate and adaptive elements of type 2 immunity.
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.
Artis
David
D
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Villarino
Alejandro
A
Silverman
Michael
M
He
Weimian
W
Thornton
Elizabeth M
EM
Mu
Sharon
S
Summer
Shamin
S
Covey
Todd M
TM
Huang
Elaine
E
Yoshida
Hiroki
H
Koretzky
Gary
G
Goldschmidt
Michael
M
Wu
Gary D
GD
de Sauvage
Fred
F
Miller
Hugh R P
HR
Saris
Christiaan J M
CJ
Scott
Phillip
P
Hunter
Christopher A
CA
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
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