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Making Insulin and Staying Out of Autoimmune Trouble: The Beta-Cell Conundrum

Autoimmune type 1 diabetes (T1D) results from the intricate crosstalk of various immune cell types. CD8+ T cells dominate the pro-inflammatory milieu of islet infiltration (insulitis), and are considered as key effectors of beta-cell destruction, through the recognition of MHC Class I-peptide comple...

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Detalles Bibliográficos
Autores principales: Carré, Alexia, Mallone, Roberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039383/
https://www.ncbi.nlm.nih.gov/pubmed/33854508
http://dx.doi.org/10.3389/fimmu.2021.639682
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author Carré, Alexia
Mallone, Roberto
author_facet Carré, Alexia
Mallone, Roberto
author_sort Carré, Alexia
collection PubMed
description Autoimmune type 1 diabetes (T1D) results from the intricate crosstalk of various immune cell types. CD8+ T cells dominate the pro-inflammatory milieu of islet infiltration (insulitis), and are considered as key effectors of beta-cell destruction, through the recognition of MHC Class I-peptide complexes. The pathways generating MHC Class I-restricted antigens in beta cells are poorly documented. Given their specialized insulin secretory function, the associated granule processing and degradation pathways, basal endoplasmic reticulum stress and susceptibility to additional stressors, alternative antigen processing and presentation (APP) pathways are likely to play a significant role in the generation of the beta-cell immunopeptidome. As direct evidence is missing, we here intersect the specificities of beta-cell function and the literature about APP in other cellular models to generate some hypotheses on APPs relevant to beta cells. We further elaborate on the potential role of these pathways in T1D pathogenesis, based on the current knowledge of antigens presented by beta cells. A better understanding of these pathways may pinpoint novel mechanisms amenable to therapeutic targeting to modulate the immunogenicity of beta cells.
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spelling pubmed-80393832021-04-13 Making Insulin and Staying Out of Autoimmune Trouble: The Beta-Cell Conundrum Carré, Alexia Mallone, Roberto Front Immunol Immunology Autoimmune type 1 diabetes (T1D) results from the intricate crosstalk of various immune cell types. CD8+ T cells dominate the pro-inflammatory milieu of islet infiltration (insulitis), and are considered as key effectors of beta-cell destruction, through the recognition of MHC Class I-peptide complexes. The pathways generating MHC Class I-restricted antigens in beta cells are poorly documented. Given their specialized insulin secretory function, the associated granule processing and degradation pathways, basal endoplasmic reticulum stress and susceptibility to additional stressors, alternative antigen processing and presentation (APP) pathways are likely to play a significant role in the generation of the beta-cell immunopeptidome. As direct evidence is missing, we here intersect the specificities of beta-cell function and the literature about APP in other cellular models to generate some hypotheses on APPs relevant to beta cells. We further elaborate on the potential role of these pathways in T1D pathogenesis, based on the current knowledge of antigens presented by beta cells. A better understanding of these pathways may pinpoint novel mechanisms amenable to therapeutic targeting to modulate the immunogenicity of beta cells. Frontiers Media S.A. 2021-03-29 /pmc/articles/PMC8039383/ /pubmed/33854508 http://dx.doi.org/10.3389/fimmu.2021.639682 Text en Copyright © 2021 Carré and Mallone https://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 Immunology
Carré, Alexia
Mallone, Roberto
Making Insulin and Staying Out of Autoimmune Trouble: The Beta-Cell Conundrum
title Making Insulin and Staying Out of Autoimmune Trouble: The Beta-Cell Conundrum
title_full Making Insulin and Staying Out of Autoimmune Trouble: The Beta-Cell Conundrum
title_fullStr Making Insulin and Staying Out of Autoimmune Trouble: The Beta-Cell Conundrum
title_full_unstemmed Making Insulin and Staying Out of Autoimmune Trouble: The Beta-Cell Conundrum
title_short Making Insulin and Staying Out of Autoimmune Trouble: The Beta-Cell Conundrum
title_sort making insulin and staying out of autoimmune trouble: the beta-cell conundrum
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039383/
https://www.ncbi.nlm.nih.gov/pubmed/33854508
http://dx.doi.org/10.3389/fimmu.2021.639682
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