title: ADP-ribosylation of P2X7: a matter of life and death for regulatory T cells and natural killer T cells.
abstract: 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.
authors.affiliation: Institute of Immunology, University Medical Center, Hamburg-Eppendorf, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Rissiek
authors.forename: Friedrich
authors.initials: F
authors.lastname: Haag
authors.forename: Olivier
authors.initials: O
authors.lastname: Boyer
authors.forename: Friedrich
authors.initials: F
authors.lastname: Koch-Nolte
authors.forename: Sahil
authors.initials: S
authors.lastname: Adriouch
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000378:metabolism*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000818:Animals; D016923:Cell Death; D006801:Humans; D051379:Mice; D009243:NAD / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*
chemical_list: D058486:Receptors, Purinergic P2X7; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D036002:ADP Ribose Transferases; C000603470:ARTC2.2 protein, mouse