Blimp1 maintains regulatory T cell identity at sites of inflammation through epigenetic imprinting

ABSTRACT: Foxp3+ regulatory T (Treg) cells restrict immune pathology in inflamed tissues; however, an inflammatory environment presents a threat to Treg cell identity and function. We here establish a transcriptional signature of central nervous system (CNS) Treg cells that accumulate during experimental autoimmune encephalitis (EAE) and identify a pathway that maintains Treg cell function and identity during severe inflammation. This pathway was dependent on the transcriptional regulator Blimp1, which prevented dismantling of Foxp3 expression and "toxic" gain-of-function of Treg cells in the inflamed CNS. Blimp1 negatively regulated IL-6- and STAT3-mediated methylation of Treg cell-specific conserved non-coding sequence 2 (CNS2) in the Foxp3 locus. Consequently, CNS2 was heavily methylated when Blimp1 was ablated, leading to loss of Foxp3 expression and severe disease. These findings identify a Blimp1-dependent epigenetic pathway that preserves Treg cell stability in inflamed non-lymphoid tissues.

ORGANISM(S): Mus musculus

PROVIDER: GSE121764 | GEO | 2018/10/26

REPOSITORIES: GEO