Interleukin 27 signaling pathways in regulation of immune and autoimmune responses

Cytokine-mediated immunity plays a crucial role in pathogenesis of various diseases including autoimmune disease. Recently, interleukin 27 was identified, which along with interleukin 23 belongs to the interleukin 12 cytokine family. Interleukin 27 is pivotal for the induction of T helper 1 responses. Recent studies, however, revealed that interleukin 27 has an immunosuppressive property. In interleukin 27 receptor-deficient mice, various pro-inflammatory cytokines were over produced resulting in excess of immune responses. The immunosuppressive effects of interleukin 27 depend on suppression of interleukin 2 production, inhibition of the development of T helper 17 cells (a newly identified inflammatogenic T helper population), and induction of interleukin 10 production. Activation of signal transducers and activators of transcription 1 and 3 is critical in the immunosuppressive function of interleukin 27. Interleukin 27 suppresses some diseases of autoimmune or allergic origin, demonstrating its promising potential in therapy of diseases mediated by inflammatory cytokines. (C) 2008 Elsevier Ltd. All rights reserved.