Cytokines play key roles in the pathogenesis of autoimmune diseases. They activate intracellular signaling pathways via receptors on the cell membrane, and tyrosine kinases are the primary mediators of this stimulation. In particular, members of the Janus kinase (JAK) family are important for signaling pathways and have been implicated in the pathogenesis of autoimmune diseases. Helper T cell development is regulated by various cytokines and the balance between Th1, Th2, and Th17 development is primarily determined by the cytokine milieu and by signals transduced by cytokines. Tofacitinib (CP-690,550), a selective inhibitor of JAKs, has been shown to suppress the production of IL-17 and IFN-γ from human CD4+ T cells. Furthermore, JAK inhibition may confer a regulatory phenotype on CD4+ T cells. JAK3 is exclusively expressed in hematopoietic cells and is essential for signaling through cytokine receptors that use a common γ-chain. Activated JAK3-deficient CD4+ T cells produce IL-10 and display an immune-regulatory phenotype. In this review, we discuss the effect of JAK inhibition on effector T cell function as well as the possibility of the induction of a regulatory phenotype by tofacitinib.
The Japanese Society of Inflammation and Regeneration