Center for Reproductive Medicine, Department of Reproductive Endocrinology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang 310014, China.
Center for Reproductive Medicine, Department of Reproductive Endocrinology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang 310014, China.
Int Immunopharmacol. 2024 Oct 25;140:112724. doi: 10.1016/j.intimp.2024.112724. Epub 2024 Aug 3.
Autoimmune diseases (ADs) are among the most significant health complications, with their incidence rising in recent years. Type 1 diabetes (T1D), an AD, targets the insulin-producing β cells in the pancreas, leading to chronic insulin deficiency in genetically susceptible individuals. Regulatory immune cells, particularly T-cells (Tregs), have been shown to play a crucial role in the pathogenesis of diabetes by modulating immune responses. In diabetic patients, Tregs often exhibit diminished effectiveness due to various factors, such as instability in forkhead box P3 (Foxp3) expression or abnormal production of the proinflammatory cytokine interferon-gamma (IFN-γ) by autoreactive T-cells. Consequently, Tregs represent a potential therapeutic target for diabetes treatment. Building on the successful clinical outcomes of chimeric antigen receptor (CAR) T-cell therapy in cancer treatment, particularly in leukemias, the concept of designing and utilizing CAR Tregs for ADs has emerged. This review summarizes the findings on Treg targeting in T1D and discusses the benefits and limitations of this treatment approach for patients suffering from T1D.
自身免疫性疾病(ADs)是最严重的健康并发症之一,近年来其发病率呈上升趋势。1 型糖尿病(T1D)是一种 AD,其靶标是胰腺中产生胰岛素的β细胞,导致遗传易感个体的慢性胰岛素缺乏。调节性免疫细胞,特别是 T 细胞(Tregs),通过调节免疫反应,在糖尿病的发病机制中发挥着至关重要的作用。在糖尿病患者中,Tregs 由于多种因素的影响,通常表现出效力降低,例如 Foxp3 表达不稳定或自身反应性 T 细胞异常产生促炎细胞因子干扰素-γ(IFN-γ)。因此,Tregs 是糖尿病治疗的一个潜在治疗靶点。基于嵌合抗原受体(CAR)T 细胞疗法在癌症治疗中的成功临床结果,特别是在白血病中的应用,设计和利用 CAR Tregs 治疗 AD 的概念已经出现。本综述总结了 T1D 中 Treg 靶向治疗的研究结果,并讨论了该治疗方法对 T1D 患者的益处和局限性。