Histone H3K27me3 demethylases regulate human Th17 cell development and effector functions by impacting on metabolism.

ABSTRACT: T helper (Th) cells are CD4⁺ effector T cells that play a critical role in immunity by shaping the inflammatory cytokine environment in a variety of physiological and pathological situations. Using a combined chemico-genetic approach, we identify histone H3K27 demethylases KDM6A and KDM6B as central regulators of human Th subsets. The prototypic KDM6 inhibitor GSK-J4 increases genome-wide levels of the repressive H3K27me3 chromatin mark and leads to suppression of the key transcription factor RORγt during Th17 differentiation. In mature Th17 cells, GSK-J4 induces an altered transcriptional program with a profound metabolic reprogramming and concomitant suppression of IL-17 cytokine levels and reduced proliferation. Single-cell analysis reveals a specific shift from highly inflam

SUBMITTER: Cribbs AP 

PROVIDER: S-EPMC7084125 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature