Human Islet Transplant Laboratory, Department of Surgery, D5.5736, Royal Victoria Hospital, McGill University Health Centre, 1001 Boulevard Décarie, Montréal, QC, H4A 3J1, Canada.
Canadian Donation and Transplantation Research Program, Edmonton, Alberta, T6G 2E1, Canada.
Curr Diab Rep. 2019 Jul 31;19(9):69. doi: 10.1007/s11892-019-1193-7.
Theories about the pathogenesis of type 1 diabetes (T1D) refer to the potential of primary islet inflammatory signaling as a trigger for the loss of self-tolerance leading to disease onset. Emerging evidence suggests that extracellular vesicles (EV) may represent the missing link between inflammation and autoimmunity. Here, we review the evidence for a role of EV in the pathogenesis of T1D, as well as discuss their potential value in the clinical sphere, as biomarkers and therapeutic agents.
EV derived from β cells are enriched in diabetogenic autoantigens and miRNAs that are selectively sorted and packaged. These EV play a pivotal role in antigen presentation and cell to cell communication leading to activation of autoimmune responses. Furthermore, recent evidence suggests the potential of EV as novel tools in clinical diagnostics and therapeutic interventions. In-depth analysis of EV cargo using modern multi-parametric technologies may be useful in enhancing our understanding of EV-mediated immune mechanisms and in identifying robust biomarkers and therapeutic strategies for T1D.
1 型糖尿病(T1D)发病机制的理论指出,原发性胰岛炎症信号可能是导致自身免疫耐受丧失从而引发疾病的一个潜在触发因素。新出现的证据表明,细胞外囊泡(EV)可能是炎症与自身免疫之间缺失的环节。在这里,我们综述了 EV 在 T1D 发病机制中的作用的证据,并讨论了它们作为生物标志物和治疗剂在临床领域的潜在价值。
β细胞衍生的 EV 富含致糖尿病自身抗原和 miRNA,这些抗原和 miRNA 被选择性地分拣和包装。这些 EV 在抗原呈递和细胞间通讯中发挥关键作用,导致自身免疫反应的激活。此外,最近的证据表明,EV 具有作为临床诊断和治疗干预新工具的潜力。使用现代多参数技术对 EV 货物进行深入分析,可能有助于我们更好地了解 EV 介导的免疫机制,并确定用于 T1D 的稳健生物标志物和治疗策略。