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Title: Evaluation of the expression and function of the P2X7 receptor and ART1 in human regulatory T-cell subsets
Authors: Cortés Garcia, Juan Diego
López López, Cintya
Cortez Espinosa, Nancy
García Hernández, Mariana H.
Guzmán Flores, Juan Manuel
Layseca Espinosa, Esther
Portales Cervantesa, Liliana
Portales Pérez, Diana Patricia
Keywords: P2X7 receptor
immune regulation
Issue Date: Jan-2016
Publisher: Elsevier GmbH
Citation: Cortés-Garcia JD, López-López C, Cortez-Espinosa N, García-Hernández MH, Guzmán-Flores JM, Layseca-Espinosa E., Portales-Cervantes L, Portales-Pérez DP. Evaluation of the expression and function of the P2X7 receptor and ART1 in human regulatory T-cell subsets. Immunobiology. 2016 Jan;221(1):84-93. doi: 10.1016/j.imbio.2015.07.018. Epub 2015 Jul 29.
Series/Report no.: Immunobiology.;Vol. 221. Número1. Pags. 84-93
Abstract: Regulatory T cells that express CD39 (CD39+ Treg) exhibit specific immunomodulatory properties. Ectonucleotidase CD39 hydrolyses ATP and ADP. ATP is a ligand of the P2X7 receptor and induces the shedding of CD62L and apoptosis. However, the role of ATP in CD39+ Treg cells has not been defined. Furthermore, NAD can activate the P2X7 receptor via ADP-ribosyltransferase (ART) enzymes and cause cell depletion in murine models. We evaluated the expression and function of P2X7 and ART1 in CD39+ Treg and CD39- Treg cells in the presence or absence of ATP and NAD. We isolated peripheral blood mononuclear cells from healthy subjects and purified CD4+ T cells, CD4+ CD25+ T cells and CD4+ CD25+ CD39+ T cells. P2X7 and ART1 expression was assessed by flow cytometry and real-time PCR. Our results showed low P2X7 expression on CD39+ Treg cells and higher levels of ART1 expression in CD4+ CD39+ T cells than the other subtypes studied. Neither shedding of CD62L nor cell death of CD39+ Treg or CD39- Treg cells was observed by 1mM ATP or 60μM NAD. In contrast, P2Xs receptor-dependent proliferation with 300μM ATP, was inhibited by NAD in the different cell types analysed. The NAD proliferation-inhibition was increased with P2Xs and A2a agonist and was reversed with P2Xs and A2a antagonist, therefore NAD inhibits P2Xs-dependent proliferation and A2a activation. In conclusion, our results suggest that the altered function and expression of P2X7 and ART1 in the human CD39+ Treg or CD39- Treg cells could participate in the resistance against cell death induced by ATP or NAD.
ISSN: 0171-2985
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