title: The WSX-1 pathway restrains intestinal T-cell immunity.
abstract: Mechanisms regulating intestinal T-cell accumulation during inflammation have considerable therapeutic value. In this study, LPS increased Staphylococcus aureus enterotoxin A-specific T cells in the gut through induction of IL-12 family members. Mice deficient in IL-12 (p35(-/-)) favored T(h)17 differentiation in lamina propria, whereas mice lacking both IL-12 and IL-23 (p40(-/-)) produced significantly fewer T(h)17 cells. However, serum analysis revealed that IL-27p28 was much higher and sustained following LPS injection than other IL-12 family cytokines. Strikingly, WSX-1 (IL-27Rα) deficiency resulted in log-fold increases in lamina propria T(h)17 cells without affecting T(h)1 numbers. These results may be explained by increased expression of α4β7 on WSX-1-deficient T cells after immunization. WSX-1-deficient regulatory T cells (Tregs) were also perturbed, producing more IL-17 and less IL-10 than wild-type Tregs. Thus, IL-27 blockade may provide a new pathway to improve mucosal vaccination.
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: McAleer
authors.forename: Christiaan J M
authors.initials: CJ
authors.lastname: Saris
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Vella
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D053759:Interleukin-23 / Q000235:genetics / Q000276:immunology; D007422:Intestines / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology*; D018123:Receptors, Interleukin; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; C484747:Il27ra protein, mouse; D053759:Interleukin-23; D008070:Lipopolysaccharides; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D018664:Interleukin-12