Bromodomain and extra-terminal protein inhibitors modulate natural killer cell function and differentiation.

ABSTRACT: Natural killer (NK) cells are integral to the innate immune system, playing a crucial role in immune surveillance and the rapid response to virally infected and tumor cells. Epigenetic gene expression regulation significantly influences NK cell function and differentiation. Using a high-throughput small-molecule drug screening approach, we identified bromodomain and extra-terminal domain (BET) inhibitors (BETi) as potent modulators of NK cell function, reducing proinflammatory cytokine secretion while increasing markers of NK cell maturation and cytotoxicity. During NK lineage specification from hematopoietic stem cells, we demonstrated that BETi reduced NK cell fate and promoted increased myeloid cell differentiation. Moreover, differentiated NK cell types had more functionally differenti

SUBMITTER: Geanes ES 

PROVIDER: S-EPMC12835054 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature