Tissue and Biomedical Engineering Laboratory, Leonard M. Miller School of Medicine, Diabetes Research Institute, University of Miami, Miami, FL, United States.
Front Immunol. 2021 Aug 20;12:722979. doi: 10.3389/fimmu.2021.722979. eCollection 2021.
The immunopathology of type I diabetes (T1D) presents a complicated case in part because of the multifactorial origin of this disease. Typically, T1D is thought to occur as a result of autoimmunity toward islets of Langerhans, resulting in the destruction of insulin-producing cells (β cells) and thus lifelong reliance on exogenous insulin. However, that explanation obscures much of the underlying mechanism, and the actual precipitating events along with the associated actors (latent viral infection, diverse immune cell types and their roles) are not completely understood. Notably, there is a malfunctioning in the regulation of cytotoxic CD8+ T cells that target endocrine cells through antigen-mediated attack. Further examination has revealed the likelihood of an imbalance in distinct subpopulations of tolerogenic and cytotoxic natural killer (NK) cells that may be the catalyst of adaptive immune system malfunction. The contributions of components outside the immune system, including environmental factors such as chronic viral infection also need more consideration, and much of the recent literature investigating the origins of this disease have focused on these factors. In this review, the details of the immunopathology of T1D regarding NK cell disfunction is discussed, along with how those mechanisms stand within the context of general autoimmune disorders. Finally, the rarer cases of latent autoimmune, COVID-19 (viral), and immune checkpoint inhibitor (ICI) induced diabetes are discussed as their exceptional pathology offers insight into the evolution of the disease as a whole.
1 型糖尿病（T1D）的免疫病理学在某种程度上呈现出复杂的情况，部分原因是这种疾病的多因素起源。通常认为，T1D 是由于针对胰岛的自身免疫反应引起的，导致产生胰岛素的细胞（β 细胞）被破坏，从而终生依赖外源性胰岛素。然而，这种解释掩盖了许多潜在的机制，实际的触发事件以及相关的参与者（潜在的病毒感染、多种免疫细胞类型及其作用）并没有完全被理解。值得注意的是，针对内分泌细胞的细胞毒性 CD8+T 细胞的调节出现了故障，通过抗原介导的攻击。进一步的研究表明，可能存在调节性和细胞毒性自然杀伤（NK）细胞亚群的失衡，这可能是适应性免疫系统功能障碍的催化剂。免疫系统以外的成分的贡献，包括慢性病毒感染等环境因素，也需要更多的考虑，最近许多研究这种疾病起源的文献都集中在这些因素上。在这篇综述中，讨论了 T1D 的免疫病理学中 NK 细胞功能障碍的细节，以及这些机制在一般自身免疫性疾病中的地位。最后，还讨论了罕见的潜伏性自身免疫性疾病、COVID-19（病毒）和免疫检查点抑制剂（ICI）诱导的糖尿病，因为它们异常的病理学为整个疾病的发展提供了深入的了解。
