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Islet stress, degradation and autoimmunity

β‐cell destruction in type 1 diabetes (T1D) results from the effect of inflammation and autoimmunity. In response to inflammatory signals, islet cells engage adaptive mechanisms to restore and maintain cellular homeostasis. Among these mechanisms, the unfolded protein response (UPR) leads to a reduc...

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Autores principales: Thomaidou, Sofia, Zaldumbide, Arnaud, Roep, Bart O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174957/
https://www.ncbi.nlm.nih.gov/pubmed/30230178
http://dx.doi.org/10.1111/dom.13387
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author Thomaidou, Sofia
Zaldumbide, Arnaud
Roep, Bart O.
author_facet Thomaidou, Sofia
Zaldumbide, Arnaud
Roep, Bart O.
author_sort Thomaidou, Sofia
collection PubMed
description β‐cell destruction in type 1 diabetes (T1D) results from the effect of inflammation and autoimmunity. In response to inflammatory signals, islet cells engage adaptive mechanisms to restore and maintain cellular homeostasis. Among these mechanisms, the unfolded protein response (UPR) leads to a reduction of the general protein translation rate, increased production of endoplasmic reticulum chaperones and the initiation of degradation by activation of the ER associated degradation pathway (ERAD) in which newly synthetized proteins are ubiquitinylated and processed through the proteasome. This adaptive phase is also believed to play a critical role in the development of autoimmunity by the generation of neoantigens. While we have previously investigated the effect of stress on transcription, translation and post‐translational events as possible source for neoantigens, the participation of the degradation machinery, yet crucial in the generation of antigenic peptides, remains to be investigated in the context of T1D pathology. In this review, we will describe the relation between the unfolded protein response and the Ubiquitin Proteasome System (UPS) and address the role of the cellular degradation machinery in the generation of antigens. Learning from tumour immunology, we propose how these processes may unmask β‐cells by triggering the generation of aberrant peptides recognized by the immune cells.
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spelling pubmed-61749572018-10-15 Islet stress, degradation and autoimmunity Thomaidou, Sofia Zaldumbide, Arnaud Roep, Bart O. Diabetes Obes Metab Review Articles β‐cell destruction in type 1 diabetes (T1D) results from the effect of inflammation and autoimmunity. In response to inflammatory signals, islet cells engage adaptive mechanisms to restore and maintain cellular homeostasis. Among these mechanisms, the unfolded protein response (UPR) leads to a reduction of the general protein translation rate, increased production of endoplasmic reticulum chaperones and the initiation of degradation by activation of the ER associated degradation pathway (ERAD) in which newly synthetized proteins are ubiquitinylated and processed through the proteasome. This adaptive phase is also believed to play a critical role in the development of autoimmunity by the generation of neoantigens. While we have previously investigated the effect of stress on transcription, translation and post‐translational events as possible source for neoantigens, the participation of the degradation machinery, yet crucial in the generation of antigenic peptides, remains to be investigated in the context of T1D pathology. In this review, we will describe the relation between the unfolded protein response and the Ubiquitin Proteasome System (UPS) and address the role of the cellular degradation machinery in the generation of antigens. Learning from tumour immunology, we propose how these processes may unmask β‐cells by triggering the generation of aberrant peptides recognized by the immune cells. Blackwell Publishing Ltd 2018-09-19 2018-09 /pmc/articles/PMC6174957/ /pubmed/30230178 http://dx.doi.org/10.1111/dom.13387 Text en © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley ' Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Review Articles
Thomaidou, Sofia
Zaldumbide, Arnaud
Roep, Bart O.
Islet stress, degradation and autoimmunity
title Islet stress, degradation and autoimmunity
title_full Islet stress, degradation and autoimmunity
title_fullStr Islet stress, degradation and autoimmunity
title_full_unstemmed Islet stress, degradation and autoimmunity
title_short Islet stress, degradation and autoimmunity
title_sort islet stress, degradation and autoimmunity
topic Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174957/
https://www.ncbi.nlm.nih.gov/pubmed/30230178
http://dx.doi.org/10.1111/dom.13387
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