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Engineered RBCs Encapsulating Antigen Induce Multi-Modal Antigen-Specific Tolerance and Protect Against Type 1 Diabetes
Antigen-specific therapies that suppress autoreactive T cells without inducing systemic immunosuppression are a much-needed treatment for autoimmune diseases, yet effective strategies remain elusive. We describe a microfluidic Cell Squeeze(®) technology to engineer red blood cells (RBCs) encapsulati...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014265/ https://www.ncbi.nlm.nih.gov/pubmed/35444659 http://dx.doi.org/10.3389/fimmu.2022.869669 |
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author | Raposo, Colin J. Cserny, Judith D. Serena, Gloria Chow, Jonathan N. Cho, Patricia Liu, Hanyang Kotler, David Sharei, Armon Bernstein, Howard John, Shinu |
author_facet | Raposo, Colin J. Cserny, Judith D. Serena, Gloria Chow, Jonathan N. Cho, Patricia Liu, Hanyang Kotler, David Sharei, Armon Bernstein, Howard John, Shinu |
author_sort | Raposo, Colin J. |
collection | PubMed |
description | Antigen-specific therapies that suppress autoreactive T cells without inducing systemic immunosuppression are a much-needed treatment for autoimmune diseases, yet effective strategies remain elusive. We describe a microfluidic Cell Squeeze(®) technology to engineer red blood cells (RBCs) encapsulating antigens to generate tolerizing antigen carriers (TACs). TACs exploit the natural route of RBC clearance enabling tolerogenic presentation of antigens. TAC treatment led to antigen-specific T cell tolerance towards exogenous and autoantigens in immunization and adoptive transfer mouse models of type 1 diabetes (T1D), respectively. Notably, in several accelerated models of T1D, TACs prevented hyperglycemia by blunting effector functions of pathogenic T cells, particularly in the pancreas. Mechanistically, TACs led to impaired trafficking of diabetogenic T cells to the pancreas, induced deletion of autoreactive CD8 T cells and expanded antigen specific Tregs that exerted bystander suppression. Our results highlight TACs as a novel approach for reinstating immune tolerance in CD4 and CD8 mediated autoimmune diseases. |
format | Online Article Text |
id | pubmed-9014265 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90142652022-04-19 Engineered RBCs Encapsulating Antigen Induce Multi-Modal Antigen-Specific Tolerance and Protect Against Type 1 Diabetes Raposo, Colin J. Cserny, Judith D. Serena, Gloria Chow, Jonathan N. Cho, Patricia Liu, Hanyang Kotler, David Sharei, Armon Bernstein, Howard John, Shinu Front Immunol Immunology Antigen-specific therapies that suppress autoreactive T cells without inducing systemic immunosuppression are a much-needed treatment for autoimmune diseases, yet effective strategies remain elusive. We describe a microfluidic Cell Squeeze(®) technology to engineer red blood cells (RBCs) encapsulating antigens to generate tolerizing antigen carriers (TACs). TACs exploit the natural route of RBC clearance enabling tolerogenic presentation of antigens. TAC treatment led to antigen-specific T cell tolerance towards exogenous and autoantigens in immunization and adoptive transfer mouse models of type 1 diabetes (T1D), respectively. Notably, in several accelerated models of T1D, TACs prevented hyperglycemia by blunting effector functions of pathogenic T cells, particularly in the pancreas. Mechanistically, TACs led to impaired trafficking of diabetogenic T cells to the pancreas, induced deletion of autoreactive CD8 T cells and expanded antigen specific Tregs that exerted bystander suppression. Our results highlight TACs as a novel approach for reinstating immune tolerance in CD4 and CD8 mediated autoimmune diseases. Frontiers Media S.A. 2022-04-04 /pmc/articles/PMC9014265/ /pubmed/35444659 http://dx.doi.org/10.3389/fimmu.2022.869669 Text en Copyright © 2022 Raposo, Cserny, Serena, Chow, Cho, Liu, Kotler, Sharei, Bernstein and John 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 Raposo, Colin J. Cserny, Judith D. Serena, Gloria Chow, Jonathan N. Cho, Patricia Liu, Hanyang Kotler, David Sharei, Armon Bernstein, Howard John, Shinu Engineered RBCs Encapsulating Antigen Induce Multi-Modal Antigen-Specific Tolerance and Protect Against Type 1 Diabetes |
title | Engineered RBCs Encapsulating Antigen Induce Multi-Modal Antigen-Specific Tolerance and Protect Against Type 1 Diabetes |
title_full | Engineered RBCs Encapsulating Antigen Induce Multi-Modal Antigen-Specific Tolerance and Protect Against Type 1 Diabetes |
title_fullStr | Engineered RBCs Encapsulating Antigen Induce Multi-Modal Antigen-Specific Tolerance and Protect Against Type 1 Diabetes |
title_full_unstemmed | Engineered RBCs Encapsulating Antigen Induce Multi-Modal Antigen-Specific Tolerance and Protect Against Type 1 Diabetes |
title_short | Engineered RBCs Encapsulating Antigen Induce Multi-Modal Antigen-Specific Tolerance and Protect Against Type 1 Diabetes |
title_sort | engineered rbcs encapsulating antigen induce multi-modal antigen-specific tolerance and protect against type 1 diabetes |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014265/ https://www.ncbi.nlm.nih.gov/pubmed/35444659 http://dx.doi.org/10.3389/fimmu.2022.869669 |
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