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 Th17 differentiation in lamina propria, whereas mice lacking both IL-12 and IL-23 (p40-/-) produced significantly fewer Th17 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 Th17 cells without affecting Th1 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. © The Japanese Society for Immunology. 2011. All rights reserved.