Cargando…
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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1783361396064387072 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6174957 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT thomaidousofia isletstressdegradationandautoimmunity AT zaldumbidearnaud isletstressdegradationandautoimmunity AT roepbarto isletstressdegradationandautoimmunity |