ROR?t-driven TH17 Cell Differentiation Requires Epigenetic Control by the Swi/Snf Chromatin Remodeling Complex.

ABSTRACT: Epigenetic regulation, including chromatin accessibility and posttranslational modifications of histones, is of importance for T cell lineage decision. TH17 cells play a critical role in protective mucosal immunity and pathogenic multiple autoimmune diseases. The differentiation of TH17 cells is dictated by a master transcription factor, ROR?t. However, the epigenetic mechanism that controls TH17 cell differentiation remains poorly understood. Here we show that the Swi/Snf complex is required for TH17-mediated cytokine production both in vitro and in vivo. We demonstrate that ROR?t recruits and forms a complex with the Swi/Snf complex to cooperate for the ROR?t-mediated epigenetic modifications of target genes, including both permissive and repressive ones for TH17 cell differentiation. Our findings thus highlight the Swi/Snf complex as an essential epigenetic regulator of TH17 cell differentiation and provide a basis for the understanding of how a master transcription factor ROR?t collaborates with the Swi/Snf complex to govern epigenetic regulation.

SUBMITTER: Lee S 

PROVIDER: S-EPMC7235640 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature