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Regulatory T Cell Extracellular Vesicles Modify T-Effector Cell Cytokine Production and Protect Against Human Skin Allograft Damage
Regulatory T cells (Tregs) are a subpopulation of CD4(+) T cells with a fundamental role in maintaining immune homeostasis and inhibiting unwanted immune responses using several different mechanisms. Recently, the intercellular transfer of molecules between Tregs and their target cells has been show...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251034/ https://www.ncbi.nlm.nih.gov/pubmed/32509778 http://dx.doi.org/10.3389/fcell.2020.00317 |
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author | Tung, Sim Lai Fanelli, Giorgia Matthews, Robert Ian Bazoer, Jordan Letizia, Marilena Vizcay-Barrena, Gema Faruqu, Farid N. Philippeos, Christina Hannen, Rosalind Al-Jamal, Khuloud T. Lombardi, Giovanna Smyth, Lesley Ann |
author_facet | Tung, Sim Lai Fanelli, Giorgia Matthews, Robert Ian Bazoer, Jordan Letizia, Marilena Vizcay-Barrena, Gema Faruqu, Farid N. Philippeos, Christina Hannen, Rosalind Al-Jamal, Khuloud T. Lombardi, Giovanna Smyth, Lesley Ann |
author_sort | Tung, Sim Lai |
collection | PubMed |
description | Regulatory T cells (Tregs) are a subpopulation of CD4(+) T cells with a fundamental role in maintaining immune homeostasis and inhibiting unwanted immune responses using several different mechanisms. Recently, the intercellular transfer of molecules between Tregs and their target cells has been shown via trogocytosis and the release of small extracellular vesicles (sEVs). In this study, CD4(+)CD25(+)CD127(lo) human Tregs were found to produce sEVs capable of inhibiting the proliferation of effector T cells (Teffs) in a dose dependent manner. These vesicles also modified the cytokine profile of Teffs leading to an increase in the production of IL-4 and IL-10 whilst simultaneously decreasing the levels of IL-6, IL-2, and IFNγ. MicroRNAs found enriched in the Treg EVs were indirectly linked to the changes in the cytokine profile observed. In a humanized mouse skin transplant model, human Treg derived EVs inhibited alloimmune-mediated skin tissue damage by limiting immune cell infiltration. Taken together, Treg sEVs may represent an exciting cell-free therapy to promote transplant survival. |
format | Online Article Text |
id | pubmed-7251034 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72510342020-06-05 Regulatory T Cell Extracellular Vesicles Modify T-Effector Cell Cytokine Production and Protect Against Human Skin Allograft Damage Tung, Sim Lai Fanelli, Giorgia Matthews, Robert Ian Bazoer, Jordan Letizia, Marilena Vizcay-Barrena, Gema Faruqu, Farid N. Philippeos, Christina Hannen, Rosalind Al-Jamal, Khuloud T. Lombardi, Giovanna Smyth, Lesley Ann Front Cell Dev Biol Cell and Developmental Biology Regulatory T cells (Tregs) are a subpopulation of CD4(+) T cells with a fundamental role in maintaining immune homeostasis and inhibiting unwanted immune responses using several different mechanisms. Recently, the intercellular transfer of molecules between Tregs and their target cells has been shown via trogocytosis and the release of small extracellular vesicles (sEVs). In this study, CD4(+)CD25(+)CD127(lo) human Tregs were found to produce sEVs capable of inhibiting the proliferation of effector T cells (Teffs) in a dose dependent manner. These vesicles also modified the cytokine profile of Teffs leading to an increase in the production of IL-4 and IL-10 whilst simultaneously decreasing the levels of IL-6, IL-2, and IFNγ. MicroRNAs found enriched in the Treg EVs were indirectly linked to the changes in the cytokine profile observed. In a humanized mouse skin transplant model, human Treg derived EVs inhibited alloimmune-mediated skin tissue damage by limiting immune cell infiltration. Taken together, Treg sEVs may represent an exciting cell-free therapy to promote transplant survival. Frontiers Media S.A. 2020-05-20 /pmc/articles/PMC7251034/ /pubmed/32509778 http://dx.doi.org/10.3389/fcell.2020.00317 Text en Copyright © 2020 Tung, Fanelli, Matthews, Bazoer, Letizia, Vizcay-Barrena, Faruqu, Philippeos, Hannen, Al-Jamal, Lombardi and Smyth. 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 | Cell and Developmental Biology Tung, Sim Lai Fanelli, Giorgia Matthews, Robert Ian Bazoer, Jordan Letizia, Marilena Vizcay-Barrena, Gema Faruqu, Farid N. Philippeos, Christina Hannen, Rosalind Al-Jamal, Khuloud T. Lombardi, Giovanna Smyth, Lesley Ann Regulatory T Cell Extracellular Vesicles Modify T-Effector Cell Cytokine Production and Protect Against Human Skin Allograft Damage |
title | Regulatory T Cell Extracellular Vesicles Modify T-Effector Cell Cytokine Production and Protect Against Human Skin Allograft Damage |
title_full | Regulatory T Cell Extracellular Vesicles Modify T-Effector Cell Cytokine Production and Protect Against Human Skin Allograft Damage |
title_fullStr | Regulatory T Cell Extracellular Vesicles Modify T-Effector Cell Cytokine Production and Protect Against Human Skin Allograft Damage |
title_full_unstemmed | Regulatory T Cell Extracellular Vesicles Modify T-Effector Cell Cytokine Production and Protect Against Human Skin Allograft Damage |
title_short | Regulatory T Cell Extracellular Vesicles Modify T-Effector Cell Cytokine Production and Protect Against Human Skin Allograft Damage |
title_sort | regulatory t cell extracellular vesicles modify t-effector cell cytokine production and protect against human skin allograft damage |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251034/ https://www.ncbi.nlm.nih.gov/pubmed/32509778 http://dx.doi.org/10.3389/fcell.2020.00317 |
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