Endogenous mitochondrial double-stranded RNA is not an activator of the type I interferon response in human pancreatic beta cells.

Autor: Coomans de Brachène A; ULB Center for Diabetes Research, Medical Faculty, Campus Erasme, Université Libre de Bruxelles (ULB), Route de Lennik, 808-CP618, 1070, Brussels, Belgium. alcooman@ulb.ac.be., Castela A; ULB Center for Diabetes Research, Medical Faculty, Campus Erasme, Université Libre de Bruxelles (ULB), Route de Lennik, 808-CP618, 1070, Brussels, Belgium., Musuaya AE; ULB Center for Diabetes Research, Medical Faculty, Campus Erasme, Université Libre de Bruxelles (ULB), Route de Lennik, 808-CP618, 1070, Brussels, Belgium., Marselli L; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy., Marchetti P; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy., Eizirik DL; ULB Center for Diabetes Research, Medical Faculty, Campus Erasme, Université Libre de Bruxelles (ULB), Route de Lennik, 808-CP618, 1070, Brussels, Belgium.; Indiana Biosciences Research Institute, Indianapolis, IN, USA.
Jazyk: angličtina
Zdroj: Auto- immunity highlights [Auto Immun Highlights] 2021 Mar 27; Vol. 12 (1), pp. 6. Date of Electronic Publication: 2021 Mar 27.
DOI: 10.1186/s13317-021-00148-2
Abstrakt: Background: Type 1 diabetes (T1D) is an autoimmune disease characterized by the progressive destruction of pancreatic beta cells. Interferon-α (IFNα), an antiviral cytokine, is expressed in the pancreatic islets in early T1D, which may be secondary to viral infections. However, not all patients harboring a type I IFN signature present signals of viral infection, suggesting that this response might be initiated by other "danger signals". Accumulation of mitochondrial double-stranded RNA (mtdsRNA; a danger signal), secondary to silencing of members of the mitochondrial degradosome, PNPT1 and SUV3, has been described to activate the innate immune response.
Methods: To evaluate whether mtdsRNA represents a "danger signal" for pancreatic beta cells in the context of T1D, we silenced PNPT1 and/or SUV3 in slowly proliferating human insulin-secreting EndoC-βH1 cells and in non-proliferating primary human beta cells and evaluated dsRNA accumulation by immunofluorescence and the type I IFN response by western blotting and RT-qPCR.
Results: Only the simultaneous silencing of PNPT1/SUV3 induced dsRNA accumulation in EndoC-βH1 cells but not in dispersed human islets, and there was no induction of a type I IFN response. By contrast, silencing of these two genes individually was enough to induce dsRNA accumulation in fibroblasts present in the human islet preparations.
Conclusions: These data suggest that accumulation of endogenous mtdsRNA following degradosome knockdown depends on the proliferative capacity of the cells and is not a mediator of the type I IFN response in human pancreatic beta cells.
Databáze: MEDLINE
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