美国威斯康星大学麦迪逊分校Feyza Engin研究团队的一项最新工作发现，IRE1α敲除引起的胰岛B细胞去分化可预防1型糖尿病（T1D）。该项研究成果于2020年3月26日在线发表在《细胞—代谢》杂志上。

Title: Beta Cell Dedifferentiation Induced by IRE1α Deletion Prevents Type 1 Diabetes

Author: Hugo Lee, Yong-Syu Lee, Quincy Harenda, Stefan Pietrzak, Hülya Zeynep Oktay, Sierra Schreiber, Yian Liao, Shreyash Sonthalia, Ashley E. Ciecko, Yi-Guang Chen, Sunduz Keles, Rupa Sridharan, Feyza Engin

Issue&Volume: 2020-03-26

Abstract: Immune-mediated destruction of insulin-producing β cells causes type 1 diabetes (T1D).However, how β cells participate in their own destruction during the disease processis poorly understood. Here, we report that modulating the unfolded protein response(UPR) in β cells of non-obese diabetic (NOD) mice by deleting the UPR sensor IRE1αprior to insulitis induced a transient dedifferentiation of β cells, resulting insubstantially reduced islet immune cell infiltration and β cell apoptosis. Single-celland whole-islet transcriptomics analyses of immature β cells revealed remarkably diminishedexpression of β cell autoantigens and MHC class I components, and upregulation ofimmune inhibitory markers. IRE1α-deficient mice exhibited significantly fewer cytotoxicCD8+ T cells in their pancreata, and adoptive transfer of their total T cells did notinduce diabetes in Rag1/ mice. Our results indicate that inducing β cell dedifferentiation, prior to insulitis,allows these cells to escape immune-mediated destruction and may be used as a novelpreventive strategy for T1D in high-risk individuals.

DOI: 10.1016/j.cmet.2020.03.002

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30117-0