MEF2D sustains activation of effector Foxp3+ Tregs during transplant survival and anticancer immunity.

ABSTRACT: The transcription factor MEF2D is important in the regulation of differentiation and adaptive responses in many cell types. We found that among T cells, MEF2D gained new functions in Foxp3+ T regulatory (Treg) cells due to its interactions with the transcription factor Foxp3 and its release from canonical partners, like histone/protein deacetylases. Though not necessary for the generation and maintenance of Tregs, MEF2D was required for the expression of IL-10, CTLA4, and Icos, and for the acquisition of an effector Treg phenotype. At these loci, MEF2D acted both synergistically and additively to Foxp3, and downstream of Blimp1. Mice with the conditional deletion in Tregs of the gene encoding MEF2D were unable to maintain long-term allograft survival despite costimulation blockade, had enh

SUBMITTER: Di Giorgio E 

PROVIDER: S-EPMC7685736 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature