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Peptide-MHC-Based Nanomedicines for the Treatment of Autoimmunity: Engineering, Mechanisms, and Diseases
The development of autoimmunity results from a breakdown of immunoregulation and involves cellularly complex immune responses against broad repertoires of epitope specificities. As a result, selective targeting of specific effector autoreactive T- or B-cells is not a realistic therapeutic option for...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870702/ https://www.ncbi.nlm.nih.gov/pubmed/33574822 http://dx.doi.org/10.3389/fimmu.2020.621774 |
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author | Serra, Pau Santamaria, Pere |
author_facet | Serra, Pau Santamaria, Pere |
author_sort | Serra, Pau |
collection | PubMed |
description | The development of autoimmunity results from a breakdown of immunoregulation and involves cellularly complex immune responses against broad repertoires of epitope specificities. As a result, selective targeting of specific effector autoreactive T- or B-cells is not a realistic therapeutic option for most autoimmune diseases. Induction of autoantigen-specific regulatory T-cells capable of effecting bystander (dominant), yet tissue-specific, immunoregulation has thus emerged as a preferred therapeutic alternative. We have shown that peptide-major histocompatibility complex (pMHC)-based nanomedicines can re-program cognate autoantigen-experienced T-cells into disease-suppressing regulatory T-cells, which in turn elicit the formation of complex regulatory cell networks capable of comprehensively suppressing organ-specific autoimmunity without impairing normal immunity. Here, we summarize the various pMHC-based nanomedicines and disease models tested to date, the engineering principles underpinning the pharmacodynamic and therapeutic potency of these compounds, and the underlying mechanisms of action. |
format | Online Article Text |
id | pubmed-7870702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78707022021-02-10 Peptide-MHC-Based Nanomedicines for the Treatment of Autoimmunity: Engineering, Mechanisms, and Diseases Serra, Pau Santamaria, Pere Front Immunol Immunology The development of autoimmunity results from a breakdown of immunoregulation and involves cellularly complex immune responses against broad repertoires of epitope specificities. As a result, selective targeting of specific effector autoreactive T- or B-cells is not a realistic therapeutic option for most autoimmune diseases. Induction of autoantigen-specific regulatory T-cells capable of effecting bystander (dominant), yet tissue-specific, immunoregulation has thus emerged as a preferred therapeutic alternative. We have shown that peptide-major histocompatibility complex (pMHC)-based nanomedicines can re-program cognate autoantigen-experienced T-cells into disease-suppressing regulatory T-cells, which in turn elicit the formation of complex regulatory cell networks capable of comprehensively suppressing organ-specific autoimmunity without impairing normal immunity. Here, we summarize the various pMHC-based nanomedicines and disease models tested to date, the engineering principles underpinning the pharmacodynamic and therapeutic potency of these compounds, and the underlying mechanisms of action. Frontiers Media S.A. 2021-01-26 /pmc/articles/PMC7870702/ /pubmed/33574822 http://dx.doi.org/10.3389/fimmu.2020.621774 Text en Copyright © 2021 Serra and Santamaria 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 | Immunology Serra, Pau Santamaria, Pere Peptide-MHC-Based Nanomedicines for the Treatment of Autoimmunity: Engineering, Mechanisms, and Diseases |
title | Peptide-MHC-Based Nanomedicines for the Treatment of Autoimmunity: Engineering, Mechanisms, and Diseases |
title_full | Peptide-MHC-Based Nanomedicines for the Treatment of Autoimmunity: Engineering, Mechanisms, and Diseases |
title_fullStr | Peptide-MHC-Based Nanomedicines for the Treatment of Autoimmunity: Engineering, Mechanisms, and Diseases |
title_full_unstemmed | Peptide-MHC-Based Nanomedicines for the Treatment of Autoimmunity: Engineering, Mechanisms, and Diseases |
title_short | Peptide-MHC-Based Nanomedicines for the Treatment of Autoimmunity: Engineering, Mechanisms, and Diseases |
title_sort | peptide-mhc-based nanomedicines for the treatment of autoimmunity: engineering, mechanisms, and diseases |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870702/ https://www.ncbi.nlm.nih.gov/pubmed/33574822 http://dx.doi.org/10.3389/fimmu.2020.621774 |
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