Targeting Tregs in T1DM: bridging heterogeneity, mechanisms, and clinical progress

Regulatory T cells (Tregs) play a pivotal role in maintaining immune tolerance and sustaining immunological homeostasis. Emerging evidence indicates that Treg characteristics and functional alterations can significantly contribute to the pathogenesis of autoimmune diseases including type 1 diabetes mellitus (T1DM). Notably, recent studies have established a positive correlation between diminished numbers of Tregs and the onset of T1DM. Although targeting Tregs has emerged as an attractive therapeutic strategy for T1DM, the heterogeneity and mechanistic complexities of Tregs remain largely unexplored and limit clinical success. We explore the dynamic alterations of Treg frequencies and phenotypes, and discuss their regulatory mechanisms throughout T1DM progression. Furthermore, we provide an overview of preclinical studies and clinical trials targeting Tregs in T1DM. By addressing translational challenges and current limitations in clinical efficacy, the ultimate aim is to develop innovative immunotherapeutic interventions for T1DM.