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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-7997429 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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