CD36-mediated ferroptosis destabilizes CD4+ T cell homeostasis in acute Stanford type-A aortic dissection

Abstract

Acute type A aortic dissection (ATAAD) is a lethal pathological process within the aorta with high mortality and morbidity. T lymphocytes are perturbed and implicated in the clinical outcome of ATAAD, but the exact characteristics of T cell phenotype and its underlying mechanisms in ATAAD remain poorly understood. Here we report that CD4⁺ T cells from ATAAD patients presented with a hypofunctional phenotype that was correlated with poor outcomes. Whole transcriptome profiles showed that ferroptosis and lipid binding pathways were enriched in CD4⁺ T cells. Inhibiting ferroptosis or reducing intrinsic reactive oxygen species limited CD4⁺ T cell dysfunction. Mechanistically, CD36 was elevated in CD4⁺ T cells, whose blockade effectively alleviated palmitic acid-induced ferroptosis and CD4⁺ T cell hypofunction. Therefore, targeting the CD36-ferroptosis pathway to restore the functions of CD4⁺ T cells is a promising therapeutic strategy to improve clinical outcomes in ATAAD patients.