@article {542326, title = {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.}, journal = {J Immunol}, volume = {183}, number = {2}, year = {2009}, month = {2009 Jul 15}, pages = {797-801}, 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.}, keywords = {Animals, Antigens, Differentiation, T-Lymphocyte, Cell Differentiation, Inducible T-Cell Co-Stimulator Protein, Interleukin-10, Interleukins, Mice, Proto-Oncogene Proteins c-maf, T-Lymphocytes, Regulatory, Transcriptional Activation}, issn = {1550-6606}, doi = {10.4049/jimmunol.0901233}, author = {Pot, Caroline and Jin, Hulin and Awasthi, Amit and Liu, Sue Min and Lai, Chen-Yen and Madan, Rajat and Sharpe, Arlene H and Karp, Christopher L and Miaw, Shi-Chuen and Ho, I-Cheng and Kuchroo, Vijay K} }