[Immune regulation by IL-27 for therapeutic usage]

Cytokine-mediated immunity plays a crucial role in the pathogenesis of various diseases including autoimmunity. Recently, IL-27 was identified, which along with IL-12, 23 and 35 belongs to the IL-12 cytokine family. These family members play roles in regulation of Th cell differentiation. IL-27 is unique in that while it induces Th1 differentiation, the same cytokine suppresses immune responses. In the absence of IL-27-mediated immunosuppression, hyper-production of various pro-inflammatory cytokines concomitant with severe inflammation in affected organs was observed in IL-27 receptor alpha chain (WSX-1)-deficient mice infected with Trypanosoma cruzi. Experimental allergic or inflammatory responses were also enhanced in WSX-1-deficient mice. The immunosuppressive effects of IL-27 depend on inhibition of the development of Th 17 cells (a newly identified inflammatory T helper population), and induction of IL-10 production. Moreover, administration of IL-27 or augmentation of IL-27 signaling suppresses some diseases of autoimmune or allergic origin, including encephalitis, arthritis, and systemic lupus erythematosus, demonstrating its potential in therapy of diseases mediated by inflammatory cytokines.