期刊
FRONTIERS IN IMMUNOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.669492
关键词
endoplasmic reticulum; ER stress; mitochondria; Type 1 diabetes (T1D); beta-cell; inflammation; cytokines
类别
资金
- DON Foundation
- Dutch Diabetes Research Foundation
- IMI2-JU [115797, 945268]
- Union's Horizon 2020 research and innovation program
- Leona M. and Harry B. Helmsley Charitable Trust
- EFPIA
- JDRF
In type 1 diabetes, beta-cell destruction is caused by inflammation and autoimmunity, with the interaction between the endoplasmic reticulum (ER) and mitochondria playing a crucial role in beta-cell dysfunction and immune activation. The crosstalk between these organelles regulates calcium homeostasis, oxidative stress, and the generation of mitochondrial-derived factors, impacting the pathogenesis of the disease.
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.
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