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Aggregated and Hyperstable Damage-Associated Molecular Patterns Are Released During ER Stress to Modulate Immune Function

Chronic ER stress occurs when protein misfolding in the Endoplasmic reticulum (ER) lumen remains unresolved despite activation of the unfolded protein response. We have shown that traumatic injury such as a severe burn leads to chronic ER stress in vivo leading to systemic inflammation which can las...

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Autores principales: Andersohn, Alexander, Garcia, M. Iveth, Fan, Ying, Thompson, Max C., Akimzhanov, Askar M., Abdullahi, Abdikarim, Jeschke, Marc G., Boehning, Darren
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759876/
https://www.ncbi.nlm.nih.gov/pubmed/31620439
http://dx.doi.org/10.3389/fcell.2019.00198
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author Andersohn, Alexander
Garcia, M. Iveth
Fan, Ying
Thompson, Max C.
Akimzhanov, Askar M.
Abdullahi, Abdikarim
Jeschke, Marc G.
Boehning, Darren
author_facet Andersohn, Alexander
Garcia, M. Iveth
Fan, Ying
Thompson, Max C.
Akimzhanov, Askar M.
Abdullahi, Abdikarim
Jeschke, Marc G.
Boehning, Darren
author_sort Andersohn, Alexander
collection PubMed
description Chronic ER stress occurs when protein misfolding in the Endoplasmic reticulum (ER) lumen remains unresolved despite activation of the unfolded protein response. We have shown that traumatic injury such as a severe burn leads to chronic ER stress in vivo leading to systemic inflammation which can last for more than a year. The mechanisms linking chronic ER stress to systemic inflammatory responses are not clear. Here we show that induction of chronic ER stress leads to the release of known and novel damage-associated molecular patterns (DAMPs). The secreted DAMPs are aggregated and markedly protease resistant. ER stress-derived DAMPs activate dendritic cells (DCs) which are then capable of polarizing naïve T cells. Our findings indicate that induction of chronic ER stress may lead to the release of hyperstable DAMPs into the circulation resulting in persistent systemic inflammation and adverse outcomes.
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spelling pubmed-67598762019-10-16 Aggregated and Hyperstable Damage-Associated Molecular Patterns Are Released During ER Stress to Modulate Immune Function Andersohn, Alexander Garcia, M. Iveth Fan, Ying Thompson, Max C. Akimzhanov, Askar M. Abdullahi, Abdikarim Jeschke, Marc G. Boehning, Darren Front Cell Dev Biol Cell and Developmental Biology Chronic ER stress occurs when protein misfolding in the Endoplasmic reticulum (ER) lumen remains unresolved despite activation of the unfolded protein response. We have shown that traumatic injury such as a severe burn leads to chronic ER stress in vivo leading to systemic inflammation which can last for more than a year. The mechanisms linking chronic ER stress to systemic inflammatory responses are not clear. Here we show that induction of chronic ER stress leads to the release of known and novel damage-associated molecular patterns (DAMPs). The secreted DAMPs are aggregated and markedly protease resistant. ER stress-derived DAMPs activate dendritic cells (DCs) which are then capable of polarizing naïve T cells. Our findings indicate that induction of chronic ER stress may lead to the release of hyperstable DAMPs into the circulation resulting in persistent systemic inflammation and adverse outcomes. Frontiers Media S.A. 2019-09-18 /pmc/articles/PMC6759876/ /pubmed/31620439 http://dx.doi.org/10.3389/fcell.2019.00198 Text en Copyright © 2019 Andersohn, Garcia, Fan, Thompson, Akimzhanov, Abdullahi, Jeschke and Boehning. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Andersohn, Alexander
Garcia, M. Iveth
Fan, Ying
Thompson, Max C.
Akimzhanov, Askar M.
Abdullahi, Abdikarim
Jeschke, Marc G.
Boehning, Darren
Aggregated and Hyperstable Damage-Associated Molecular Patterns Are Released During ER Stress to Modulate Immune Function
title Aggregated and Hyperstable Damage-Associated Molecular Patterns Are Released During ER Stress to Modulate Immune Function
title_full Aggregated and Hyperstable Damage-Associated Molecular Patterns Are Released During ER Stress to Modulate Immune Function
title_fullStr Aggregated and Hyperstable Damage-Associated Molecular Patterns Are Released During ER Stress to Modulate Immune Function
title_full_unstemmed Aggregated and Hyperstable Damage-Associated Molecular Patterns Are Released During ER Stress to Modulate Immune Function
title_short Aggregated and Hyperstable Damage-Associated Molecular Patterns Are Released During ER Stress to Modulate Immune Function
title_sort aggregated and hyperstable damage-associated molecular patterns are released during er stress to modulate immune function
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759876/
https://www.ncbi.nlm.nih.gov/pubmed/31620439
http://dx.doi.org/10.3389/fcell.2019.00198
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