Evaluation of the expression and function of the P2X7 receptor and ART1 in human regulatory T-cell subsets

被引:14
作者
Cortes-Garcia, Juan D. [1 ]
Lopez-Lopez, Cintya [2 ]
Cortez-Espinosa, Nancy [1 ]
Garcia-Hernandez, Mariana H. [3 ]
Guzman-Flores, Juan M. [1 ]
Layseca-Espinosa, Esther [4 ]
Portales-Cervantes, Liliana [1 ]
Portales-Perez, Diana P. [1 ]
机构
[1] UASLP, Fac Chem Sci, Lab Immunol & Cellular & Mol Biol, San Luis Potosi 78210, SLP, Mexico
[2] Inst Potosino Invest Cient & Tecnol, Div Mol Biol, San Luis Potosi, SLP, Mexico
[3] Unit Med Invest IMSS, Zacatecas, Zac, Mexico
[4] UASLP, Fac Med, Dept Immunol, San Luis Potosi 78210, SLP, Mexico
关键词
P2X7; receptor; ART1; ATP; NAD; Immune regulation; CD39; NICOTINAMIDE ADENINE-DINUCLEOTIDE; ECTO-ADP-RIBOSYLTRANSFERASES; P2X(7) RECEPTOR; NAD GLYCOHYDROLASE; RHEUMATOID-ARTHRITIS; PURINERGIC RECEPTOR; ATP RELEASE; ACTIVATION; RIBOSYLATION; TRANSFERASE;
D O I
10.1016/j.imbio.2015.07.018
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
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 60 mu M NAD. In contrast, P2Xs receptor-dependent proliferation with 300 p,M ATP, was inhibited by NAD in the different cell types analysed. The NAD proliferation-inhibition was increased with P2X5 and A2a agonist and was reversed with P2X5 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. (C) 2015 Elsevier GmbH. All rights reserved.
引用
收藏
页码:84 / 93
页数:10
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