Department of Anesthesiology, the Second XiangYa Hospital, Central South University, ChangSha, China.
Anesthesiology Research Institute of Central South University, ChangSha, China.
Cell Death Dis. 2024 Sep 12;15(9):669. doi: 10.1038/s41419-024-07022-9.
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.
急性 A 型主动脉夹层（ATAAD）是主动脉内一种致命的病理过程，具有高死亡率和发病率。T 淋巴细胞受到干扰，并与 ATAAD 的临床结果有关，但 T 细胞表型的确切特征及其在 ATAAD 中的潜在机制仍知之甚少。在这里，我们报告称，ATAAD 患者的 CD4 T 细胞表现出低功能表型，与不良预后相关。全转录组谱显示，铁死亡和脂质结合途径在 CD4 T 细胞中富集。抑制铁死亡或降低内源性活性氧可限制 CD4 T 细胞功能障碍。在机制上，CD36 在 CD4 T 细胞中升高，其阻断可有效缓解棕榈酸诱导的铁死亡和 CD4 T 细胞低功能。因此，靶向 CD36-铁死亡途径以恢复 CD4 T 细胞的功能是改善 ATAAD 患者临床结果的有前途的治疗策略。
