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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4913941?pdf=render |
| _version_ | 1819268020270268416 |
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| author | Dominique Fernández Felipe Flores-Santibáñez Jocelyn Neira Francisco Osorio-Barrios Gabriela Tejón Sarah Nuñez Yessia Hidalgo Maria Jose Fuenzalida Daniel Meza Gonzalo Ureta Alvaro Lladser Rodrigo Pacheco Claudio Acuña-Castillo Victoria Guixé Francisco J Quintana Maria Rosa Bono Mario Rosemblatt Daniela Sauma |
| author_facet | Dominique Fernández Felipe Flores-Santibáñez Jocelyn Neira Francisco Osorio-Barrios Gabriela Tejón Sarah Nuñez Yessia Hidalgo Maria Jose Fuenzalida Daniel Meza Gonzalo Ureta Alvaro Lladser Rodrigo Pacheco Claudio Acuña-Castillo Victoria Guixé Francisco J Quintana Maria Rosa Bono Mario Rosemblatt Daniela Sauma |
| author_sort | Dominique Fernández |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-23T21:26:25Z |
| format | Article |
| id | doaj.art-1e734191b82a4327915313039879c8e1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T21:26:25Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1e734191b82a4327915313039879c8e12022-12-21T17:30:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01116e015788910.1371/journal.pone.0157889Purinergic Signaling as a Regulator of Th17 Cell Plasticity.Dominique FernándezFelipe Flores-SantibáñezJocelyn NeiraFrancisco Osorio-BarriosGabriela TejónSarah NuñezYessia HidalgoMaria Jose FuenzalidaDaniel MezaGonzalo UretaAlvaro LladserRodrigo PachecoClaudio Acuña-CastilloVictoria GuixéFrancisco J QuintanaMaria Rosa BonoMario RosemblattDaniela SaumaT 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.http://europepmc.org/articles/PMC4913941?pdf=render |
| spellingShingle | Dominique Fernández Felipe Flores-Santibáñez Jocelyn Neira Francisco Osorio-Barrios Gabriela Tejón Sarah Nuñez Yessia Hidalgo Maria Jose Fuenzalida Daniel Meza Gonzalo Ureta Alvaro Lladser Rodrigo Pacheco Claudio Acuña-Castillo Victoria Guixé Francisco J Quintana Maria Rosa Bono Mario Rosemblatt Daniela Sauma Purinergic Signaling as a Regulator of Th17 Cell Plasticity. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC4913941?pdf=render |
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