The IL-27R (WSX-1) is required to suppress T cell hyperactivity during infection.
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.
Villarino
Alejandro
A
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce St, Philadelphia, PA 19104, USA.
Hibbert
Linda
L
Lieberman
Linda
L
Wilson
Emma
E
Mak
Tak
T
Yoshida
Hiroki
H
Kastelein
Robert A
RA
Saris
Christiaan
C
Hunter
Christopher A
CA
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
C484747:Il27ra protein, mouse; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin