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Purinergic Signaling as a Regulator of Th17 Cell Plasticity
T helper type 17 (Th17) lymphocytes, characterized by the production of interleukin-17 and other pro-inflammatory cytokines, are present in intestinal lamina propria and have been described as important players driving intestinal inflammation. Recent evidence, supporting the notion of a functional a...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913941/ https://www.ncbi.nlm.nih.gov/pubmed/27322617 http://dx.doi.org/10.1371/journal.pone.0157889 |
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author | Fernández, Dominique Flores-Santibáñez, Felipe Neira, Jocelyn Osorio-Barrios, Francisco Tejón, Gabriela Nuñez, Sarah Hidalgo, Yessia Fuenzalida, Maria Jose Meza, Daniel Ureta, Gonzalo Lladser, Alvaro Pacheco, Rodrigo Acuña-Castillo, Claudio Guixé, Victoria Quintana, Francisco J. Bono, Maria Rosa Rosemblatt, Mario Sauma, Daniela |
author_facet | Fernández, Dominique Flores-Santibáñez, Felipe Neira, Jocelyn Osorio-Barrios, Francisco Tejón, Gabriela Nuñez, Sarah Hidalgo, Yessia Fuenzalida, Maria Jose Meza, Daniel Ureta, Gonzalo Lladser, Alvaro Pacheco, Rodrigo Acuña-Castillo, Claudio Guixé, Victoria Quintana, Francisco J. Bono, Maria Rosa Rosemblatt, Mario Sauma, Daniela |
author_sort | Fernández, Dominique |
collection | PubMed |
description | T helper type 17 (Th17) lymphocytes, characterized by the production of interleukin-17 and other pro-inflammatory cytokines, are present in intestinal lamina propria and have been described as important players driving intestinal inflammation. Recent evidence, supporting the notion of a functional and phenotypic instability of Th17 cells, has shown that Th17 differentiate into type 1 regulatory (Tr1) T cells during the resolution of intestinal inflammation. Moreover, it has been suggested that the expression of CD39 ectonucleotidase endows Th17 cells with immunosuppressive properties. However, the exact role of CD39 ectonucleotidase in Th17 cells has not been studied in the context of intestinal inflammation. Here we show that Th17 cells expressing CD39 ectonucleotidase can hydrolyze ATP and survive to ATP-induced cell death. Moreover, in vitro-generated Th17 cells expressing the CD39 ectonucleotidase produce IL-10 and are less pathogenic than CD39 negative Th17 cells in a model of experimental colitis in Rag(-/-) mice. Remarkably, we show that CD39 activity regulates the conversion of Th17 cells to IL-10-producing cells in vitro, which is abrogated in the presence of ATP and the CD39-specific inhibitor ARL67156. All these data suggest that CD39 expression by Th17 cells allows the depletion of ATP and is crucial for IL-10 production and survival during the resolution of intestinal inflammation. |
format | Online Article Text |
id | pubmed-4913941 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-49139412016-07-06 Purinergic Signaling as a Regulator of Th17 Cell Plasticity Fernández, Dominique Flores-Santibáñez, Felipe Neira, Jocelyn Osorio-Barrios, Francisco Tejón, Gabriela Nuñez, Sarah Hidalgo, Yessia Fuenzalida, Maria Jose Meza, Daniel Ureta, Gonzalo Lladser, Alvaro Pacheco, Rodrigo Acuña-Castillo, Claudio Guixé, Victoria Quintana, Francisco J. Bono, Maria Rosa Rosemblatt, Mario Sauma, Daniela PLoS One Research Article T helper type 17 (Th17) lymphocytes, characterized by the production of interleukin-17 and other pro-inflammatory cytokines, are present in intestinal lamina propria and have been described as important players driving intestinal inflammation. Recent evidence, supporting the notion of a functional and phenotypic instability of Th17 cells, has shown that Th17 differentiate into type 1 regulatory (Tr1) T cells during the resolution of intestinal inflammation. Moreover, it has been suggested that the expression of CD39 ectonucleotidase endows Th17 cells with immunosuppressive properties. However, the exact role of CD39 ectonucleotidase in Th17 cells has not been studied in the context of intestinal inflammation. Here we show that Th17 cells expressing CD39 ectonucleotidase can hydrolyze ATP and survive to ATP-induced cell death. Moreover, in vitro-generated Th17 cells expressing the CD39 ectonucleotidase produce IL-10 and are less pathogenic than CD39 negative Th17 cells in a model of experimental colitis in Rag(-/-) mice. Remarkably, we show that CD39 activity regulates the conversion of Th17 cells to IL-10-producing cells in vitro, which is abrogated in the presence of ATP and the CD39-specific inhibitor ARL67156. All these data suggest that CD39 expression by Th17 cells allows the depletion of ATP and is crucial for IL-10 production and survival during the resolution of intestinal inflammation. Public Library of Science 2016-06-20 /pmc/articles/PMC4913941/ /pubmed/27322617 http://dx.doi.org/10.1371/journal.pone.0157889 Text en © 2016 Fernández et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Fernández, Dominique Flores-Santibáñez, Felipe Neira, Jocelyn Osorio-Barrios, Francisco Tejón, Gabriela Nuñez, Sarah Hidalgo, Yessia Fuenzalida, Maria Jose Meza, Daniel Ureta, Gonzalo Lladser, Alvaro Pacheco, Rodrigo Acuña-Castillo, Claudio Guixé, Victoria Quintana, Francisco J. Bono, Maria Rosa Rosemblatt, Mario Sauma, Daniela Purinergic Signaling as a Regulator of Th17 Cell Plasticity |
title | Purinergic Signaling as a Regulator of Th17 Cell Plasticity |
title_full | Purinergic Signaling as a Regulator of Th17 Cell Plasticity |
title_fullStr | Purinergic Signaling as a Regulator of Th17 Cell Plasticity |
title_full_unstemmed | Purinergic Signaling as a Regulator of Th17 Cell Plasticity |
title_short | Purinergic Signaling as a Regulator of Th17 Cell Plasticity |
title_sort | purinergic signaling as a regulator of th17 cell plasticity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913941/ https://www.ncbi.nlm.nih.gov/pubmed/27322617 http://dx.doi.org/10.1371/journal.pone.0157889 |
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