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The Conserved Non-coding Sequences CNS6 and CNS9 Control Cytokine-Induced Rorc Transcription during T Helper 17 Cell Differentiation.
- Source :
-
Immunity (10747613) . Sep2020, Vol. 53 Issue 3, p614-614. 1p. - Publication Year :
- 2020
-
Abstract
- RORγt 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-β, 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 RORγt expression in innate lymphocytes and γδ 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 RORγt expression and epigenetic activation of the Rorc locus. TGF-β alone was sufficient to induce RORγt 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-β in regulation of RORγt expression and Th17 cell commitment via distinct cis -regulatory elements. • CNS6 and CNS9 are not required for RORγt expression in innate immune cells • Deficiency in CNS6 or CNS9 decreases Th17 cell differentiation and EAE disease • CNS9 and, to a lesser extent, CNS6 are required for IL-6-induced RORγt expression • CNS6, but not CNS9, is indispensable for TGF-β-induced RORγt expression IL-6 and TGF-β induce Th17 cell differentiation. Chang et al. demonstrate that these two cytokines initiate Th17 cell differentiation by inducing de novo Rorc transcription via the distinct conserved non-coding sequences CNS6 and CNS9. [ABSTRACT FROM AUTHOR]
- Subjects :
- *T helper cells
*CELL differentiation
*SMAD proteins
*T cells
*CELL determination
Subjects
Details
- Language :
- English
- ISSN :
- 10747613
- Volume :
- 53
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Immunity (10747613)
- Publication Type :
- Academic Journal
- Accession number :
- 145677074
- Full Text :
- https://doi.org/10.1016/j.immuni.2020.07.012