ADP-Ribosylation of P2X7 - A Matter of Life and Death for Regulatory T Cells and Natural Killer T Cells
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ADP-Ribosylation of P2X7 - A Matter of Life and Death for Regulatory T Cells and Natural Killer T Cells. / Rissiek, Björn; Haag, Friedrich; Boyer, Olivier; Nolte, Friedrich; Adriouch, Sahil.
In: CURR TOP MICROBIOL, Vol. 384, 2015, p. 107-126.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - ADP-Ribosylation of P2X7 - A Matter of Life and Death for Regulatory T Cells and Natural Killer T Cells
AU - Rissiek, Björn
AU - Haag, Friedrich
AU - Boyer, Olivier
AU - Nolte, Friedrich
AU - Adriouch, Sahil
PY - 2015
Y1 - 2015
N2 - ADP-ribosyltransferases comprise a family of enzymes originally discovered as bacterial toxins and later characterised also in mammals. In mice, the ADP-ribosyltransferase ARTC2.2 is expressed at the surface of T lymphocytes and has been studied extensively. In the presence of extracellular NAD(+), ARTC2.2 ADP-ribosylates several cell surface target proteins and thereby regulates their function. P2X7, an ATP-gated cation channel, has been discovered as a prominent ARTC2.2 target at the surface of mouse T cells. ADP-ribosylation of P2X7 in the presence of low micromolar extracellular NAD(+) induces long-lasting P2X7 activation and triggers cell death. Regulatory T cell subsets (Tregs and NKT cells) are remarkably sensitive to NAD(+)-induced cell death (NICD). Thus, liberation of endogenous NAD(+) by stressed cells is now viewed as a danger signal promoting immune responses by hindering regulatory T cells. This review will highlight the recent discoveries on the in vivo role of the ARTC2.2/P2X7 pathway triggered by the endogenous release of extracellular NAD(+), the relative sensitivity of lymphocytes subsets to this regulatory pathway and its pharmacological manipulation using camelid-derived ARTC2.2-blocking nanobodies.
AB - ADP-ribosyltransferases comprise a family of enzymes originally discovered as bacterial toxins and later characterised also in mammals. In mice, the ADP-ribosyltransferase ARTC2.2 is expressed at the surface of T lymphocytes and has been studied extensively. In the presence of extracellular NAD(+), ARTC2.2 ADP-ribosylates several cell surface target proteins and thereby regulates their function. P2X7, an ATP-gated cation channel, has been discovered as a prominent ARTC2.2 target at the surface of mouse T cells. ADP-ribosylation of P2X7 in the presence of low micromolar extracellular NAD(+) induces long-lasting P2X7 activation and triggers cell death. Regulatory T cell subsets (Tregs and NKT cells) are remarkably sensitive to NAD(+)-induced cell death (NICD). Thus, liberation of endogenous NAD(+) by stressed cells is now viewed as a danger signal promoting immune responses by hindering regulatory T cells. This review will highlight the recent discoveries on the in vivo role of the ARTC2.2/P2X7 pathway triggered by the endogenous release of extracellular NAD(+), the relative sensitivity of lymphocytes subsets to this regulatory pathway and its pharmacological manipulation using camelid-derived ARTC2.2-blocking nanobodies.
U2 - 10.1007/82_2014_420
DO - 10.1007/82_2014_420
M3 - SCORING: Journal article
C2 - 25048544
VL - 384
SP - 107
EP - 126
JO - CURR TOP MICROBIOL
JF - CURR TOP MICROBIOL
SN - 0070-217X
ER -
