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Caroline Pot, Hulin Jin, Amit Awasthi, Sue Min Liu, Chen-Yen Lai, Rajat Madan, Arlene H Sharpe, Christopher L Karp, Shi-Chuen Miaw, I-Cheng Ho, Vijay K Kuchroo, 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, The Journal of Immunology, Volume 183, Issue 2, July 2009, Pages 797–801, https://doi.org/10.4049/jimmunol.0901233
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Abstract
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.