Article
Evaluation of the expression and function of the P2X7 receptor and ART1 in human regulatory T-cell subsets
Registro en:
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.
0171-2985
dx.doi.org/10.1016/j.imbio.2015.07.018
Autor
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
Institución
Resumen
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. Laboratory of Immunology and Cellular and Molecular Biology, Faculty of Chemical Sciences, UASLP, San Luis Potosí, S.L.P., Mexico
Division of Molecular Biology, Instituto Potosino de Investigación Científica y Tecnológica, San Luis Potosí, S.L.P. Mexico
Unit of Medicine Investigation IMSS, Zacatecas, Zac, Mexico
Department of Immunology, Faculty of Medicine, UASLP, San Luis Potosí, S.L.P. Mexico