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, Vol. 52, No. 11, 11.2022, p. 1805-1818.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -