The Role of the Histone Methyltransferase Enhancer of Zeste Homolog 2 (EZH2) in the Pathobiological Mechanisms Underlying Inflammatory Bowel Disease (IBD).

ABSTRACT: Regulatory T (Treg) cells expressing the transcription factor FOXP3 play a pivotal role in maintaining immunologic self-tolerance. We and others have shown previously that EZH2 is recruited to the FOXP3 promoter and its targets in Treg cells. To further address the role for EZH2 in Treg cellular function, we have now generated mice that lack EZH2 specifically in Treg cells (EZH2^Δ/ΔFOXP3⁺). We find that EZH2 deficiency in FOXP3⁺ T cells results in lethal multiorgan autoimmunity. We further demonstrate that EZH2^Δ/ΔFOXP3⁺ T cells lack a regulatory phenotype in vitro and secrete proinflammatory cytokines. Of special interest, EZH2^Δ/ΔFOXP3⁺ mice develop spontaneous inflammatory bowel disease. Guided by these results, w

SUBMITTER: Sarmento OF 

PROVIDER: S-EPMC5241744 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature