Pot, CarolineCarolinePotJin, HulinHulinJinAwasthi, AmitAmitAwasthiLiu, Sue MinSue MinLiuLai, Chen-YenChen-YenLaiMadan, RajatRajatMadanSharpe, Arlene HArlene HSharpeKarp, Christopher LChristopher LKarpSHI-CHUEN MIAWHo, I-ChengI-ChengHoKuchroo, Vijay KVijay KKuchroo2019-08-062019-08-062009-07-150022-1767https://www.scopus.com/inward/record.uri?eid=2-s2.0-69249083836&doi=10.4049%2fjimmunol.0901233&partnerID=40&md5=18fbba6846d911042cb202b5b85679f9https://scholars.lib.ntu.edu.tw/handle/123456789/416264IL-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.enjournal article10.4049/jimmunol.0901233195708262-s2.0-69249083836WOS:000267812600003https://api.elsevier.com/content/abstract/scopus_id/69249083836