PT - JOURNAL ARTICLE AU - Pot, Caroline AU - Jin, Hulin AU - Awasthi, Amit AU - Liu, Sue Min AU - Lai, Chen-Yen AU - Madan, Rajat AU - Sharpe, Arlene H. AU - Karp, Christopher L. AU - Miaw, Shi-Chuen AU - Ho, I-Cheng AU - Kuchroo, Vijay K. TI - Cutting Edge: IL-27 Induces the Transcription Factor c-Maf, Cytokine IL-21, and the Costimulatory Receptor ICOS that Coordinately Act Together to Promote Differentiation of IL-10-Producing Tr1 Cells AID - 10.4049/jimmunol.0901233 DP - 2009 Jul 15 TA - The Journal of Immunology PG - 797--801 VI - 183 IP - 2 4099 - http://www.jimmunol.org/content/183/2/797.short 4100 - http://www.jimmunol.org/content/183/2/797.full SO - J. Immunol.2009 Jul 15; 183 AB - IL-27 has recently been identified as a differentiation factor for the generation of IL-10-producing regulatory type 1 (Tr1) T cells. However, how IL-27 induces the expansion of Tr1 cells has not been elucidated. In this study we demonstrate that IL-27 drives the expansion and differentiation of IL-10-producing murine Tr1 cells by inducing three key elements: the transcription factor c-Maf, the cytokine IL-21, and the costimulatory receptor ICOS. IL-27-driven c-Maf expression transactivates IL-21 production, which acts as an autocrine growth factor for the expansion and/or maintenance of IL-27-induced Tr1 cells. ICOS further promotes IL-27-driven Tr1 cells. Each of those elements is essential, because loss of c-Maf, IL-21-signaling, or ICOS decreases the frequency of IL-27-induced differentiation of IL-10-producing Tr1 cells.