The WSX-1 pathway restrains intestinal T-cell immunity

• Published in: International immunology 2011-02, Vol.23 (2), p.129-137
• Main Authors: McAleer, Jeremy P, Saris, Christiaan J M, Vella, Anthony T
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - pharmacology; Animals; Flow Cytometry; Gene Expression Regulation - drug effects; Interleukin-12 - genetics; Interleukin-12 - immunology; Interleukin-23 - genetics; Interleukin-23 - immunology; Intestines - immunology; Lipopolysaccharides - pharmacology; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Cytokine - genetics; Receptors, Cytokine - immunology; Signal Transduction; Staphylococcus aureus; T-Lymphocytes - drug effects; T-Lymphocytes - immunology
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxq464

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.