Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands.
Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands.
Front Immunol. 2021 Apr 16;12:669492. doi: 10.3389/fimmu.2021.669492. eCollection 2021.
Beta-cell destruction in type 1 diabetes (T1D) results from the combined effect of inflammation and recurrent autoimmunity. In response to inflammatory signals, beta-cells engage adaptive mechanisms where the endoplasmic reticulum (ER) and mitochondria act in concert to restore cellular homeostasis. In the recent years it has become clear that this adaptive phase may trigger the development of autoimmunity by the generation of autoantigens recognized by autoreactive CD8 T cells. The participation of the ER stress and the unfolded protein response to the increased visibility of beta-cells to the immune system has been largely described. However, the role of the other cellular organelles, and in particular the mitochondria that are central mediator for beta-cell survival and function, remains poorly investigated. In this review we will dissect the crosstalk between the ER and mitochondria in the context of T1D, highlighting the key role played by this interaction in beta-cell dysfunctions and immune activation, especially through regulation of calcium homeostasis, oxidative stress and generation of mitochondrial-derived factors.
1 型糖尿病（T1D）中的β细胞破坏是炎症和反复自身免疫共同作用的结果。β细胞在炎症信号的刺激下，会通过内质网（ER）和线粒体协同作用来恢复细胞内稳态的适应性机制。近年来，人们已经清楚地认识到，这种适应性阶段可能通过产生被自身反应性 CD8 T 细胞识别的自身抗原而引发自身免疫。内质网应激和未折叠蛋白反应使β细胞对免疫系统的可见性增加，这一过程已经得到了广泛的描述。然而，其他细胞细胞器，特别是作为β细胞存活和功能的核心介质的线粒体的作用，仍未得到充分研究。在这篇综述中，我们将剖析 T1D 中 ER 和线粒体之间的相互作用，强调这种相互作用在β细胞功能障碍和免疫激活中的关键作用，特别是通过调节钙稳态、氧化应激和线粒体衍生因子的产生。
