ER stress induced mitochondrial dysfunction drives Treg instability in coronary artery disease.

ABSTRACT: Under conditions of chronic unresolved inflammation characteristic of atherosclerosis, regulatory CD4⁺ T cells (Tregs) become unstable and convert to cytotoxic exTregs. The mechanism driving this conversion in humans is unclear. Here, we show unresolved endoplasmic reticulum (ER) stress as a key factor driving Treg instability. Human exTregs undergo ER stress and consequent mitochondrial dysfunction that remains unchecked due to defective mitophagy. Integrated stress response (ISR), a pathway that can trigger inflammatory signaling, is also upregulated in exTregs. exTregs are highly apoptotic and are more susceptible to stress-mediated cellular dysfunction due to their senescent state. In a phenotype reminiscent of exTregs, Tregs from coronary artery disease (CAD) patients show

SUBMITTER: Parashar S 

PROVIDER: S-EPMC12686412 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature