| First Author | Chang D | Year | 2020 |
| Journal | Immunity | Volume | 53 |
| Issue | 3 | Pages | 614-626.e4 |
| PubMed ID | 32827457 | Mgi Jnum | J:305606 |
| Mgi Id | MGI:6706476 | Doi | 10.1016/j.immuni.2020.07.012 |
| Citation | Chang D, et al. (2020) The Conserved Non-coding Sequences CNS6 and CNS9 Control Cytokine-Induced Rorc Transcription during T Helper 17 Cell Differentiation. Immunity 53(3):614-626.e4 |
| abstractText | RORgammat 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 RORgammat expression in innate lymphocytes and gammadelta 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 RORgammat expression and epigenetic activation of the Rorc locus. TGF-beta alone was sufficient to induce RORgammat 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 RORgammat expression and Th17 cell commitment via distinct cis-regulatory elements. |
