IL-27 and IFN- α Signal via Stat1 and Stat3 and Induce T-Bet and IL-12R β 2 in Naive T Cells

Interleukin-27 (IL-27) supports proliferation of naive CD4 super(+) T cells and enhances interferon- gamma (IFN- gamma ) production by activated T cells and natural killer (NK) cells. We report here that IL-27 induces Stat1 and Stat3 phosphorylation and activation in human and murine cell lines and primary human T cells. IL-27 also induces T-Bet, a Stat1-dependent gene crucial to Th1 cell commitment. Similarly, IFN- alpha activates Stat1 and Stat3 and T-Bet expression in naive T cells. Induction of T-Bet results in upregulation of IL-12R beta 2 on naive T cells, which is essential for responsiveness to IL-12 and differentiation to a Th1 phenotype. Both IL-27 and IFN- alpha induce expression of IL-12R beta 2 in T cells. In contrast, IFN- gamma , which activates Stat1 but not Stat3, induces expression of T-Bet but not IL-12R beta 2 in naive T cells. We propose that IL-27 and IFN- alpha are important for early Th1 commitment and act upstream of IL-12 and IFN- gamma in this pathway.