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Induction of Antigen-Specific Tolerance in Autoimmune Diabetes with Nanoparticles Containing Hybrid Insulin Peptides

Autoreactive T cells are thought to orchestrate the onset and progression of autoimmune diabetes. Key cognate antigens of these diabetogenic T cells include hybrid insulin peptides, formed by the fusion of insulin fragments to cleavage products of other β-cell granule proteins. Here we review initia...

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Autores principales: DiLisio, James E., Haskins, Kathryn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997429/
https://www.ncbi.nlm.nih.gov/pubmed/33673706
http://dx.doi.org/10.3390/biomedicines9030240
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author DiLisio, James E.
Haskins, Kathryn
author_facet DiLisio, James E.
Haskins, Kathryn
author_sort DiLisio, James E.
collection PubMed
description Autoreactive T cells are thought to orchestrate the onset and progression of autoimmune diabetes. Key cognate antigens of these diabetogenic T cells include hybrid insulin peptides, formed by the fusion of insulin fragments to cleavage products of other β-cell granule proteins. Here we review initial work exploring tolerance induction to a hybrid insulin peptide using a biodegradable, nanoparticle delivery system in non-obese diabetic (NOD) mice. The immune phenotype(s) and possible mechanism(s) behind antigen-specific tolerance induction were dissected with a disease transfer model using transgenic autoreactive mouse T cells. Treatment of NOD mice with peptide-coupled nanoparticles appeared to have a dual function in preventing diabetes onset, inducing anergy in effector T cells and enhancing the activity of regulatory T cells. Importantly, the ratio of these two cell types in the pancreas was pushed toward tolerance. Antigen-specific tolerance induction to hybrid insulin peptides has the translational potential to preserve islet β-cells in new-onset or at-risk patients and prevent recurrent autoimmunity in transplant patients.
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spelling pubmed-79974292021-03-27 Induction of Antigen-Specific Tolerance in Autoimmune Diabetes with Nanoparticles Containing Hybrid Insulin Peptides DiLisio, James E. Haskins, Kathryn Biomedicines Review Autoreactive T cells are thought to orchestrate the onset and progression of autoimmune diabetes. Key cognate antigens of these diabetogenic T cells include hybrid insulin peptides, formed by the fusion of insulin fragments to cleavage products of other β-cell granule proteins. Here we review initial work exploring tolerance induction to a hybrid insulin peptide using a biodegradable, nanoparticle delivery system in non-obese diabetic (NOD) mice. The immune phenotype(s) and possible mechanism(s) behind antigen-specific tolerance induction were dissected with a disease transfer model using transgenic autoreactive mouse T cells. Treatment of NOD mice with peptide-coupled nanoparticles appeared to have a dual function in preventing diabetes onset, inducing anergy in effector T cells and enhancing the activity of regulatory T cells. Importantly, the ratio of these two cell types in the pancreas was pushed toward tolerance. Antigen-specific tolerance induction to hybrid insulin peptides has the translational potential to preserve islet β-cells in new-onset or at-risk patients and prevent recurrent autoimmunity in transplant patients. MDPI 2021-02-27 /pmc/articles/PMC7997429/ /pubmed/33673706 http://dx.doi.org/10.3390/biomedicines9030240 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Review
DiLisio, James E.
Haskins, Kathryn
Induction of Antigen-Specific Tolerance in Autoimmune Diabetes with Nanoparticles Containing Hybrid Insulin Peptides
title Induction of Antigen-Specific Tolerance in Autoimmune Diabetes with Nanoparticles Containing Hybrid Insulin Peptides
title_full Induction of Antigen-Specific Tolerance in Autoimmune Diabetes with Nanoparticles Containing Hybrid Insulin Peptides
title_fullStr Induction of Antigen-Specific Tolerance in Autoimmune Diabetes with Nanoparticles Containing Hybrid Insulin Peptides
title_full_unstemmed Induction of Antigen-Specific Tolerance in Autoimmune Diabetes with Nanoparticles Containing Hybrid Insulin Peptides
title_short Induction of Antigen-Specific Tolerance in Autoimmune Diabetes with Nanoparticles Containing Hybrid Insulin Peptides
title_sort induction of antigen-specific tolerance in autoimmune diabetes with nanoparticles containing hybrid insulin peptides
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997429/
https://www.ncbi.nlm.nih.gov/pubmed/33673706
http://dx.doi.org/10.3390/biomedicines9030240
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