Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by pancreatic islet inflammation (insulitis) and specific pancreatic β-cell destruction by an immune attack. Although the precise underlying mechanisms leading to the autoimmune assault remain poorly understood, it is well accepted that insulitis takes place in the context of a conflicting dialogue between pancreatic β-cells and the immune cells. Moreover, both host genetic background (i.e., candidate genes) and environmental factors (e.g., viral infections) contribute to this inadequate dialogue. Accumulating evidence indicates that type I interferons (IFNs), cytokines that are crucial for both innate and adaptive immune responses, act as key links between environmental and genetic risk factors in the development of T1D. This chapter summarizes some relevant pathways involved in β-cell dysfunction and death, and briefly reviews how enteroviral infections and genetic susceptibility can impact insulitis. Moreover, we present the current evidence showing that, in β-cells, type I IFN signaling pathway activation leads to several outcomes, such as long-lasting major histocompatibility complex (MHC) class I hyperexpression, endoplasmic reticulum (ER) stress, epigenetic changes, and induction of posttranscriptional as well as posttranslational modifications. MHC class I overexpression, when combined with ER stress and posttranscriptional/posttranslational modifications, might lead to sustained neoantigen presentation to immune system and β-cell apoptosis. This knowledge supports the concept that type I IFNs are implicated in the early stages of T1D pathogenesis. Finally, we highlight the promising therapeutic avenues for T1D treatment directed at type I IFN signaling pathway.

1 型糖尿病 (T1D) 是一种慢性自身免疫性疾病，其特征是胰岛炎症（胰岛炎）和免疫攻击导致的特异性胰腺 β 细胞破坏。尽管导致自身免疫攻击的确切潜在机制仍然知之甚少，但人们普遍认为，胰岛炎发生在胰腺 β 细胞和免疫细胞之间冲突对话的背景下。此外，宿主遗传背景（即候选基因）和环境因素（例如病毒感染）都促成了这种不充分的对话。越来越多的证据表明，I 型干扰素 (IFN) 是对先天性和适应性免疫反应都至关重要的细胞因子，在 T1D 的发展中充当环境和遗传风险因素之间的关键联系。本章总结了与 β 细胞功能障碍和死亡有关的一些相关途径，并简要回顾了肠道病毒感染和遗传易感性如何影响胰岛炎。此外，我们目前的证据表明，在 β 细胞中，I 型 IFN 信号通路激活会导致多种结果，例如持久的主要组织相容性复合体 (MHC) I 类高表达、内质网 (ER) 应激、表观遗传变化，以及转录后和翻译后修饰的诱导。MHC I 类过表达，当与 ER 应激和转录后/翻译后修饰相结合时，可能导致持续向免疫系统呈递新抗原和 β 细胞凋亡。这一知识支持 I 型 IFN 与 T1D 发病机制的早期阶段有关的概念。最后，