Title: Dissecting the control of key checkpoints between autoimmune potential and autoimmune pathology
Other Titles: Het ontleden van de controlemechanismen van de belangrijkste checkpoints tussen autoimmune potentie en autoimmune pathologie
Authors: Tian, Lei
Issue Date: 11-Sep-2015
Abstract: Type 1 and type 2 diabetes (T1D and T2D) share pathophysiological characteristics, yet a mechanistic link has remained elusive. T1D results from the autoimmune destruction of pancreatic beta cells, while beta cell failure in T2D is a secondary event following chronic insulin resistance. Here we find a new immune-independent component of diabetes susceptibility in the T1D non-obese diabetic (NOD) mouse model. Following induced unfolded protein stress NOD and B10 islets propagated a qualitatively different, resulting in apoptosis and senescence on the NOD background, and Manf upregulation and stressed survival on the B10 background. Genetic susceptibility to transgene-induced diabetes was associated with coding polymorphisms in Xrcc4 and reduced Glis3 expression. This effect was replicated in B10 mice through an elevated fat diet or increased autoimmune burden. Together, these results demonstrate a link between T1D and T2D susceptibility in islet beta cell fragility, modulated by genetic and environmental components.
Publication status: published
KU Leuven publication type: TH
Appears in Collections:Laboratory of Genetics of Autoimmunity
Clinical and Experimental Endocrinology

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