title: The IL-27R (WSX-1) is required to suppress T cell hyperactivity during infection.
abstract: Although recent studies have described IL-27 and its receptor, WSX-1, as promoters of Th1 differentiation in naive CD4+ T cells, the data presented here indicate that signaling through this receptor is involved in limiting the intensity and duration of T cell activity. When WSX-1-deficient mice are infected with the intracellular pathogen Toxoplasma gondii, they establish protective T cell responses, characterized by production of inflammatory cytokines and control of parasite replication. However, infected WSX-1-/- mice are unable to downregulate these protective responses, and develop a lethal, T cell-mediated inflammatory disease. This pathology was characterized by the excessive production of IFN-gamma, persistence of highly activated T cells, and enhanced T cell proliferation in vivo. Together, these findings demonstrate that WSX-1 is not required for the generation of IFN-gamma-mediated immunity to this parasitic infection and identify a novel function for this receptor as a potent antagonist of T cell-mediated, immune hyperactivity.
authors: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce St, Philadelphia, PA 19104, USA.
authors: Alejandro
authors: A
authors: Villarino
authors: Linda
authors: L
authors: Hibbert
authors: Linda
authors: L
authors: Lieberman
authors: Emma
authors: E
authors: Wilson
authors: Tak
authors: T
authors: Mak
authors: Hiroki
authors: H
authors: Yoshida
authors: Robert A
authors: RA
authors: Kastelein
authors: Christiaan
authors: C
authors: Saris
authors: Christopher A
authors: CA
authors: Hunter
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D007239:Infections / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D018123:Receptors, Interleukin; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000502:physiology; D014122:Toxoplasma / Q000276:immunology; D014123:Toxoplasmosis / Q000276:immunology
chemical_list: C484747:Il27ra protein, mouse; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin