@article{3509b75a84d847eabb1a3de7af3052ff,
title = "Regulation of Pathogenic T Helper 17 Cell Differentiation by Steroid Receptor Coactivator-3",
abstract = "T helper 17 (Th17) cell development is programmed by the orphan nuclear receptor RORγt, but the underlying mechanism is not well understood. Nuclear receptor-mediated transcriptional activation depends on coactivators. Here, we show that steroid receptor coactivator-3 (SRC-3) critically regulates Th17 cell differentiation. Reduced incidence of experimental autoimmune encephalitis (EAE) associated with decreased Th17 cell generation in vivo was observed in mice with SRC-3 deletion specifically in T cells. In vitro, SRC-3 deficiency did not affect TGF-β/IL-6-induced Th17 cell generation but severely impaired pathogenic Th17 differentiation induced by IL-1/IL-6/IL-23. Microarray analysis revealed that SRC-3 not only regulates IL-17A but also IL-1R1 expression. SRC-3 bound to Il17a and Il1r1 loci in a RORγt-dependent manner and was required for recruitment of the p300 acetyltransferase. Thus, SRC-3 is critical for RORγt-dependent gene expression in Th17 cell-driven autoimmune diseases. The unique transcriptional programs in IL-1-induced inflammatory Th17 cells have remained unclear. Tanaka et al. demonstrate that SRC-3 in CD4+ T helper cells functions as a specific coactivator of RORγt, a master transcription factor of Th17 cells, by regulating IL-1-IL1R1 signaling.",
keywords = "EAE, IL17A, IL1R1, RORγt, p300, pathogenic Th17, steroid receptor coactivator-3",
author = "Kentaro Tanaka and Martinez, {Gustavo J.} and Xiaowei Yan and Weiwen Long and Kenji Ichiyama and Xinxin Chi and Kim, {Byung Seok} and Reynolds, {Joseph M.} and Yeonseok Chung and Shinya Tanaka and Lan Liao and Yoichi Nakanishi and Akihiko Yoshimura and Pan Zheng and Xiaohu Wang and Qiang Tian and Jianming Xu and O'Malley, {Bert W.} and Chen Dong",
note = "Funding Information: We thank Danielle Yi (Institute for System Biology) for her assistance with microarray analysis, all staff of the Flow Cytometry and Cellular Imaging Core Facility at MD Anderson Cancer Center for helping with cell sorting, Marzenna Bronska and Xin Lin (MD Anderson Cancer Center) for helpful discussions, Brian York (Baylor College of Medicine) for providing mice, Li Qin (Baylor College of Medicine) for technical assistance, and all of the Dong lab members and colleagues of the Research Institute for Diseases of the Chest at Kyushu University for their consistent help. This study is supported in part by grants from the NIH (to C.D.). K.T. received a fellowship grant from the SENSHIN Medical Research Foundation and is a recipient of the Institutional Program for Young Researcher Overseas Visits by Keio University and the Japan Society for the Promotion of Science. Funding Information: We thank Danielle Yi (Institute for System Biology) for her assistance with microarray analysis, all staff of the Flow Cytometry and Cellular Imaging Core Facility at MD Anderson Cancer Center for helping with cell sorting, Marzenna Bronska and Xin Lin (MD Anderson Cancer Center) for helpful discussions, Brian York (Baylor College of Medicine) for providing mice, Li Qin (Baylor College of Medicine) for technical assistance, and all of the Dong lab members and colleagues of the Research Institute for Diseases of the Chest at Kyushu University for their consistent help. This study is supported in part by grants from the NIH (to C.D.). K.T. received a fellowship grant from the SENSHIN Medical Research Foundation and is a recipient of the Institutional Program for Young Researcher Overseas Visits by Keio University and the Japan Society for the Promotion of Science . Publisher Copyright: {\textcopyright} 2018 The Author(s)",
year = "2018",
month = may,
day = "22",
doi = "10.1016/j.celrep.2018.04.088",
language = "English",
volume = "23",
pages = "2318--2329",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "8",
}