Pipella Jasmine, Motlagh Roozbeh Akbari, Rampazzo Morelli Nayara, Thompson Peter J
Children's Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada.
Department of Physiology & Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
Diabetes. 2025 Sep 1;74(9):1562-1576. doi: 10.2337/db24-1122.
Senescence is a β-cell stress response in type 1 diabetes (T1D), the origins of which are not understood. We wanted to determine the role of the T cell-mediated autoimmune process in β-cell senescence during T1D. In the nonobese diabetic mouse model, β-cell senescence largely depended on damage inflicted by autoreactive CD4+ and CD8+ T cells during the development of T1D. Chronic exposure to sublethal doses of proinflammatory cytokines associated with the diabetogenic process was sufficient to elicit stable senescence phenotypes in human islets in culture. Our findings suggest that autoreactive T cells trigger not only β-cell death but also β-cell senescence, potentially via cytokine-dependent mechanisms in T1D. This finding has implications for understanding the mechanisms of action and beneficial impacts of immunotherapy using CD3 antibodies in T1D.
衰老 是 1 型糖尿病（T1D）中的一种β细胞应激反应，其起源尚不清楚。我们想确定 T 细胞介导的自身免疫过程在 T1D 期间β细胞衰老中的作用。在非肥胖糖尿病小鼠模型中，β细胞衰老很大程度上取决于自身反应性 CD4+和 CD8+T 细胞在 T1D 发展过程中造成的损伤。长期暴露于与致糖尿病过程相关的亚致死剂量促炎细胞因子足以在培养的人胰岛中引发稳定的衰老表型。我们的研究结果表明，自身反应性 T 细胞不仅会触发β细胞死亡，还会通过 T1D 中可能的细胞因子依赖性机制引发β细胞衰老。这一发现对于理解 T1D 中使用 CD3 抗体的免疫疗法的作用机制和有益影响具有重要意义。
