| Title | The Conserved Non-coding Sequences CNS6 and CNS9 Control Cytokine-Induced Rorc Transcription during T Helper 17 Cell Differentiation |
| Authors | Chang, Dehui Xing, Qi Su, Yang Zhao, Xiaohong Xu, Wei Wang, Xiaohu Dong, Chen |
| Affiliation | Tsinghua Univ, Inst Immunol, Beijing 100084, Peoples R China Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China Peking Univ, Col Life Sci, Beijing 10084, Peoples R China Peking Univ, Peking Univ Tsinghua Univ Natl Inst Biol Sci Join, Beijing 10084, Peoples R China Beijing Key Lab Immunol Res Chron Dis, Beijing 100084, Peoples R China |
| Keywords | INNATE LYMPHOID-CELLS TGF-BETA GAMMA-T C-MAF PROINFLAMMATORY IL-17(+) IL-22 PRODUCTION DNA METHYLATION FOXP3 GENE GENERATION T(H)17 |
| Issue Date | 15-Sep-2020 |
| Publisher | IMMUNITY |
| Abstract | ROR gamma t is the lineage-specific transcription factor for T helper 17 (Th17) cells whose upregulation in developing Th17 cells is critically regulated by interleukin-6 (IL-6) and TGF-beta, the molecular mechanisms of which remain largely unknown. Here we identified conserved non-coding sequences (CNSs) 6 and 9 at the Rorc gene, essential for its expression during Th17 cell differentiation but not required for ROR gamma t expression in innate lymphocytes and gamma delta T cells. Mechanistically, the IL-6-signal transducer and activator of transcription 3 (STAT3) axis appeared to be largely dependent on CNS9 and only partially on CNS6 in controlling ROR gamma t expression and epigenetic activation of the Rorc locus. TGF-beta alone was sufficient to induce ROR gamma t expression in a CNS6- but not CNS9-dependent manner through CNS6 binding by SMAD proteins. Our study reveals an important synergistic mechanism downstream of IL-6 and TGF-beta in regulation of ROR gamma t expression and Th17 cell commitment via distinct cis-regulatory elements. |
| URI | http://hdl.handle.net/20.500.11897/591965 |
| ISSN | 1074-7613 |
| DOI | 10.1016/j.immuni.2020.07.012 |
| Indexed | SCI(E) |
| Appears in Collections: | 生命科学学院 |
