P2X7 is expressed on human innate-like T lymphocytes and mediates susceptibility to ATP-induced cell death

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P2X7 is expressed on human innate-like T lymphocytes and mediates susceptibility to ATP-induced cell death. / Winzer, Riekje; Serracant-Prat, Arnau; Brock, Valerie J; Pinto-Espinoza, Carolina; Rissiek, Björn; Amadi, Miriam; Eich, Niklas; Rissiek, Anne; Schneider, Enja; Magnus, Tim; Guse, Andreas H; Diercks, Björn-Philipp; Koch-Nolte, Friedrich; Tolosa, Eva.

in: EUR J IMMUNOL, Jahrgang 52, Nr. 11, 11.2022, S. 1805-1818.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

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@article{d1490acbf680479d92667b08275f4ac3,
title = "P2X7 is expressed on human innate-like T lymphocytes and mediates susceptibility to ATP-induced cell death",
abstract = "Extracellular ATP activates the P2X7 receptor, leading to inflammasome activation and release of pro-inflammatory cytokines in monocytes. However, a detailed analysis of P2X7 receptor expression and function in the human T cell compartment has not been reported. Here, we used a P2X7-specific nanobody to assess cell membrane expression and function of P2X7 on peripheral T lymphocyte subsets. The results show that innate-like T cells, which effectively react to innate stimuli by secreting high amounts of pro-inflammatory cytokines, have the highest expression of P2X7 in the human T cell compartment. Using Tγδ cells as example for an innate-like lymphocyte population, we demonstrate that these cells are more sensitive to P2X7 receptor activation than conventional T cells, affecting fundamental cellular mechanisms like calcium signaling and ATP-induced cell death. The increased susceptibility of innate-like T cells to P2X7-mediated cell death provides a mechanism to control their homeostasis under inflammatory conditions. Understanding the expression and function of P2X7 on human immune cells is essential to assume the benefits and consequences of newly developed P2X7-based therapeutic approaches.",
keywords = "Humans, Receptors, Purinergic P2X7/genetics, Adenosine Triphosphate/metabolism, Cell Death, Monocytes/metabolism, Cytokines/metabolism",
author = "Riekje Winzer and Arnau Serracant-Prat and Brock, {Valerie J} and Carolina Pinto-Espinoza and Bj{\"o}rn Rissiek and Miriam Amadi and Niklas Eich and Anne Rissiek and Enja Schneider and Tim Magnus and Guse, {Andreas H} and Bj{\"o}rn-Philipp Diercks and Friedrich Koch-Nolte and Eva Tolosa",
note = "{\textcopyright} 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.",
year = "2022",
month = nov,
doi = "10.1002/eji.202249932",
language = "English",
volume = "52",
pages = "1805--1818",
journal = "EUR J IMMUNOL",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag GmbH",
number = "11",

}

RIS

TY - JOUR

T1 - P2X7 is expressed on human innate-like T lymphocytes and mediates susceptibility to ATP-induced cell death

AU - Winzer, Riekje

AU - Serracant-Prat, Arnau

AU - Brock, Valerie J

AU - Pinto-Espinoza, Carolina

AU - Rissiek, Björn

AU - Amadi, Miriam

AU - Eich, Niklas

AU - Rissiek, Anne

AU - Schneider, Enja

AU - Magnus, Tim

AU - Guse, Andreas H

AU - Diercks, Björn-Philipp

AU - Koch-Nolte, Friedrich

AU - Tolosa, Eva

N1 - © 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.

PY - 2022/11

Y1 - 2022/11

N2 - Extracellular ATP activates the P2X7 receptor, leading to inflammasome activation and release of pro-inflammatory cytokines in monocytes. However, a detailed analysis of P2X7 receptor expression and function in the human T cell compartment has not been reported. Here, we used a P2X7-specific nanobody to assess cell membrane expression and function of P2X7 on peripheral T lymphocyte subsets. The results show that innate-like T cells, which effectively react to innate stimuli by secreting high amounts of pro-inflammatory cytokines, have the highest expression of P2X7 in the human T cell compartment. Using Tγδ cells as example for an innate-like lymphocyte population, we demonstrate that these cells are more sensitive to P2X7 receptor activation than conventional T cells, affecting fundamental cellular mechanisms like calcium signaling and ATP-induced cell death. The increased susceptibility of innate-like T cells to P2X7-mediated cell death provides a mechanism to control their homeostasis under inflammatory conditions. Understanding the expression and function of P2X7 on human immune cells is essential to assume the benefits and consequences of newly developed P2X7-based therapeutic approaches.

AB - Extracellular ATP activates the P2X7 receptor, leading to inflammasome activation and release of pro-inflammatory cytokines in monocytes. However, a detailed analysis of P2X7 receptor expression and function in the human T cell compartment has not been reported. Here, we used a P2X7-specific nanobody to assess cell membrane expression and function of P2X7 on peripheral T lymphocyte subsets. The results show that innate-like T cells, which effectively react to innate stimuli by secreting high amounts of pro-inflammatory cytokines, have the highest expression of P2X7 in the human T cell compartment. Using Tγδ cells as example for an innate-like lymphocyte population, we demonstrate that these cells are more sensitive to P2X7 receptor activation than conventional T cells, affecting fundamental cellular mechanisms like calcium signaling and ATP-induced cell death. The increased susceptibility of innate-like T cells to P2X7-mediated cell death provides a mechanism to control their homeostasis under inflammatory conditions. Understanding the expression and function of P2X7 on human immune cells is essential to assume the benefits and consequences of newly developed P2X7-based therapeutic approaches.

KW - Humans

KW - Receptors, Purinergic P2X7/genetics

KW - Adenosine Triphosphate/metabolism

KW - Cell Death

KW - Monocytes/metabolism

KW - Cytokines/metabolism

U2 - 10.1002/eji.202249932

DO - 10.1002/eji.202249932

M3 - SCORING: Journal article

C2 - 36178227

VL - 52

SP - 1805

EP - 1818

JO - EUR J IMMUNOL

JF - EUR J IMMUNOL

SN - 0014-2980

IS - 11

ER -