UTX Coordinates TCF1 and STAT3 to Control Progenitor CD8+ T cell Fate in Autoimmune Diabetes.

ABSTRACT: Type 1 Diabetes Mellitus (T1D) is driven by chronic autoimmune destruction of pancreatic beta cells, primarily mediated by CD8+ progenitor T cells that replenish pathogenic effectors. However, the regulatory mechanisms guiding this progenitor-to-effector transition remain unclear. T1D susceptibility has been linked to an X chromosome region (Xp13-p11) containing UTX, an epigenetic regulator. Here, we show that T cell-specific deletion of UTX in NOD mice prevents T1D, implicating UTX as a key driver of disease. UTX-deficient mice exhibit an accumulation of CD8+ progenitors and a reduction in effectors, suggesting that UTX facilitates progenitor differentiation to effectors. This function is independent of UTX's demethylase activity and instead depends on interactions with transcription fact

SUBMITTER: Chen HC 

PROVIDER: S-EPMC11702527 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature