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The Multifaceted Actions of CD73 During Development and Suppressive Actions of Regulatory T Cells
Adenosine (Ado) has been shown to have immunosuppressive effects in a variety of diseases. It can either be released directly into the extracellular environment by cells, or it can be produced by degradation of ATP within the extracellular spaces. This extracellular pathway is facilitated by the con...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197450/ https://www.ncbi.nlm.nih.gov/pubmed/35711418 http://dx.doi.org/10.3389/fimmu.2022.914799 |
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author | Da, Meihong Chen, Luxia Enk, Alexander Ring, Sabine Mahnke, Karsten |
author_facet | Da, Meihong Chen, Luxia Enk, Alexander Ring, Sabine Mahnke, Karsten |
author_sort | Da, Meihong |
collection | PubMed |
description | Adenosine (Ado) has been shown to have immunosuppressive effects in a variety of diseases. It can either be released directly into the extracellular environment by cells, or it can be produced by degradation of ATP within the extracellular spaces. This extracellular pathway is facilitated by the concerted actions of the ectoenzymes CD39 and CD73. In a first step CD39 dephosphorylates ATP to ADP and AMP, respectively, and in a second step CD73 converts AMP to Ado. Thus, activity of CD73 on the cell surface of cells is the rate limiting step in the generation of extracellular Ado. Among T cells, CD73 is most abundantly expressed by regulatory T cells (Tregs) and is even upregulated after their activation. Functionally, the generation of Ado by CD73(+) Tregs has been shown to play a role in immune suppression of dendritic cells, monocytes and T cells, and the defined expression of CD73 by Tregs in immunosuppressive environments, such as tumors, made CD73 a novel checkpoint inhibitor. Therefore, therapeutical intervention by anti-CD73 antibodies or by chemical inhibitors of the enzymatic function is currently under investigation in some preclinical animal models. In the following we summarize the expression pattern and the possible functions of CD73 in T cells and Tregs, and exemplify novel ways to manipulate CD73 functions in Tregs to stimulate anti-tumor immunity. |
format | Online Article Text |
id | pubmed-9197450 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91974502022-06-15 The Multifaceted Actions of CD73 During Development and Suppressive Actions of Regulatory T Cells Da, Meihong Chen, Luxia Enk, Alexander Ring, Sabine Mahnke, Karsten Front Immunol Immunology Adenosine (Ado) has been shown to have immunosuppressive effects in a variety of diseases. It can either be released directly into the extracellular environment by cells, or it can be produced by degradation of ATP within the extracellular spaces. This extracellular pathway is facilitated by the concerted actions of the ectoenzymes CD39 and CD73. In a first step CD39 dephosphorylates ATP to ADP and AMP, respectively, and in a second step CD73 converts AMP to Ado. Thus, activity of CD73 on the cell surface of cells is the rate limiting step in the generation of extracellular Ado. Among T cells, CD73 is most abundantly expressed by regulatory T cells (Tregs) and is even upregulated after their activation. Functionally, the generation of Ado by CD73(+) Tregs has been shown to play a role in immune suppression of dendritic cells, monocytes and T cells, and the defined expression of CD73 by Tregs in immunosuppressive environments, such as tumors, made CD73 a novel checkpoint inhibitor. Therefore, therapeutical intervention by anti-CD73 antibodies or by chemical inhibitors of the enzymatic function is currently under investigation in some preclinical animal models. In the following we summarize the expression pattern and the possible functions of CD73 in T cells and Tregs, and exemplify novel ways to manipulate CD73 functions in Tregs to stimulate anti-tumor immunity. Frontiers Media S.A. 2022-05-31 /pmc/articles/PMC9197450/ /pubmed/35711418 http://dx.doi.org/10.3389/fimmu.2022.914799 Text en Copyright © 2022 Da, Chen, Enk, Ring and Mahnke 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 Da, Meihong Chen, Luxia Enk, Alexander Ring, Sabine Mahnke, Karsten The Multifaceted Actions of CD73 During Development and Suppressive Actions of Regulatory T Cells |
title | The Multifaceted Actions of CD73 During Development and Suppressive Actions of Regulatory T Cells |
title_full | The Multifaceted Actions of CD73 During Development and Suppressive Actions of Regulatory T Cells |
title_fullStr | The Multifaceted Actions of CD73 During Development and Suppressive Actions of Regulatory T Cells |
title_full_unstemmed | The Multifaceted Actions of CD73 During Development and Suppressive Actions of Regulatory T Cells |
title_short | The Multifaceted Actions of CD73 During Development and Suppressive Actions of Regulatory T Cells |
title_sort | multifaceted actions of cd73 during development and suppressive actions of regulatory t cells |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197450/ https://www.ncbi.nlm.nih.gov/pubmed/35711418 http://dx.doi.org/10.3389/fimmu.2022.914799 |
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