Fraser Devin R, Stadnyk Andrew W
Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
Department of Pediatrics, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
Front Immunol. 2025 Jun 18;16:1602934. doi: 10.3389/fimmu.2025.1602934. eCollection 2025.
Type 1 diabetes (T1D) is a chronic autoimmune disorder characterized by autoreactive CD8 T cells that destroy insulin-producing pancreatic β-cells. CD8 T cells are unlikely to be the only cells involved in diabetes. Relatively recently described and still enigmatic, Mucosal-associated invariant T (MAIT) cells, innate-like T cells that recognize microbial-derived peptides, exist in the blood and tissues and are implicated in early immune responses. Immunological differences, some of which implicate MAIT cells, exist between individuals at different stages of T1D progression. This review explores the emerging relationship between gastrointestinal and pancreatic MAIT cell populations and the onset and progression of T1D. Early microbial colonization is critical for immune maturation, homeostasis, and MAIT cell development, and disruptions such as Caesarean delivery or antibiotic-induced dysbiosis correlate with increased T1D incidence. Diabetes progression in the diabetes-prone NOD mice is associated with reduced gut mucosal integrity, impairing the protective IL-17 and IL-22 responses of gut-resident MAIT cells and exacerbating systemic inflammation. MAIT cells recruited to the inflamed pancreas during T1D onset likely contribute to β-cell destruction through IFN-γ and granzyme B production. This hypothesis is supported by altered MAIT cell frequencies and phenotypes in individuals with T1D; MAIT cells are reduced in the blood of children recently diagnosed with T1D, potentially corresponding to pancreatic migration, while adults with long-term T1D have persistent, circulating MAIT cells with exhaustion markers. MAIT cells appear to have dual protective and pathogenic roles impacted by microbiome interactions. Understanding these relationships may inform non-invasive biomarkers for the disease.
1型糖尿病（T1D）是一种慢性自身免疫性疾病，其特征是自身反应性CD8 T细胞破坏产生胰岛素的胰腺β细胞。CD8 T细胞不太可能是参与糖尿病的唯一细胞。黏膜相关恒定T（MAIT）细胞是一种相对较新发现且仍神秘的细胞，它是识别微生物衍生肽的固有样T细胞，存在于血液和组织中，并参与早期免疫反应。在T1D进展的不同阶段，个体之间存在免疫差异，其中一些差异与MAIT细胞有关。本综述探讨了胃肠道和胰腺MAIT细胞群体与T1D发病和进展之间的新出现的关系。早期微生物定植对免疫成熟、稳态和MAIT细胞发育至关重要，剖宫产或抗生素诱导的生态失调等干扰与T1D发病率增加相关。易患糖尿病的非肥胖糖尿病（NOD）小鼠的糖尿病进展与肠道黏膜完整性降低有关，损害了肠道驻留MAIT细胞的保护性白细胞介素-17和白细胞介素-22反应，并加剧全身炎症。在T1D发病期间募集到发炎胰腺的MAIT细胞可能通过产生干扰素-γ和颗粒酶B导致β细胞破坏。这一假设得到了T1D患者MAIT细胞频率和表型改变的支持；最近诊断为T1D的儿童血液中MAIT细胞减少，这可能与胰腺迁移相对应，而长期患T1D的成年人有持续循环的带有耗竭标志物的MAIT细胞。MAIT细胞似乎具有受微生物组相互作用影响的双重保护和致病作用。了解这些关系可能为该疾病提供非侵入性生物标志物。
