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

Autor: Juan Manuel Guzmán-Flores, Liliana Portales-Cervantes, Nancy Cortez-Espinosa, Diana P. Portales-Pérez, Cintya López-López, Mariana Haydee García-Hernández, Juan D. Cortés-García, Esther Layseca-Espinosa
Rok vydání: 2016
Předmět:
Adult
Male
0301 basic medicine
Cell type
Programmed cell death
Adenosine
Adenosine A2 Receptor Agonists
Adolescent
Regulatory T cell
Primary Cell Culture
Immunology
Cell
chemical and pharmacologic phenomena
Biology
GPI-Linked Proteins
Immunophenotyping
Flow cytometry
03 medical and health sciences
Adenosine Triphosphate
Antigens
CD
T-Lymphocyte Subsets
Phenethylamines
medicine
Humans
Immunology and Allergy
IL-2 receptor
L-Selectin
Cell Proliferation
ADP Ribose Transferases
Cell Death
medicine.diagnostic_test
Receptors
Adenosine A2
Triazines
Apyrase
hemic and immune systems
Hematology
Triazoles
NAD
Molecular biology
Adenosine A2 Receptor Antagonists
030104 developmental biology
medicine.anatomical_structure
Gene Expression Regulation
Apoptosis
Female
Receptors
Purinergic P2X7
NAD+ kinase
Signal Transduction
Zdroj: Immunobiology. 221:84-93
ISSN: 0171-2985
Popis: 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.
Databáze: OpenAIRE
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