FoxP3 and Ezh2 regulate Tfr cell suppressive function and transcriptional program.

ABSTRACT: Follicular regulatory T (Tfr) cells are a regulatory T cell subset that controls antibody production by inhibiting T follicular helper (Tfh)-mediated help to B cells. Tfh and Tfr cells possess opposing functions suggesting unique programming. Here we elucidated the transcriptional program controlling Tfr suppressive function. We found that Tfr cells have a program for suppressive function fine-tuned by tissue microenvironment. The transcription factor FoxP3 and chromatin-modifying enzyme EZH2 are essential for this transcriptional program but regulate the program in distinct ways. FoxP3 modifies the Tfh program to induce a Tfr-like functional state, demonstrating that Tfr cells coopt the Tfh program for suppression. Importantly, we identified a Tfr cell population that loses the Tfr progra

SUBMITTER: Hou S 

PROVIDER: S-EPMC6400538 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature