Extracellular NAD+ shapes the Foxp3+ regulatory T cell compartment through the ART2-P2X7 pathway.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractCD4(+)CD25(+)FoxP3(+) regulatory T cells (T reg cells) play a major role in the control of immune responses but the factors controlling their homeostasis and function remain poorly characterized. Nicotinamide adenine dinucleotide (NAD(+)) released during cell damage or inflammation results in ART2.2-mediated ADP-ribosylation of the cytolytic P2X7 receptor on T cells. We show that T reg cells express the ART2.2 enzyme and high levels of P2X7 and that T reg cells can be depleted by intravenous injection of NAD(+). Moreover, lower T reg cell numbers are found in mice deficient for the NAD-hydrolase CD38 than in wild-type, P2X7-deficient, or ART2-deficient mice, indicating a role for extracellular NAD(+) in T reg cell homeostasis. Even routine cell preparation leads to release of NAD(+) in sufficient quantities to profoundly affect T reg cell viability, phenotype, and function. We demonstrate that T reg cells can be protected from the deleterious effects of NAD(+) by an inhibitory ART2.2-specific single domain antibody. Furthermore, selective depletion of T reg cells by systemic administration of NAD(+) can be used to promote an antitumor response in several mouse tumor models. Collectively, our data demonstrate that NAD(+) influences survival, phenotype, and function of T reg cells and provide proof of principle that acting on the ART2-P2X7 pathway represents a new strategy to manipulate T reg cells in vivo.
CitationExtracellular NAD+ shapes the Foxp3+ regulatory T cell compartment through the ART2-P2X7 pathway. 2010, 207 (12):2561-8 J. Exp. Med.
AffiliationInstitut National de la Santé et de la Recherche Medicale, U905, 76183 Rouen, France.
The following license files are associated with this item:
- Differential regulation of P2X7 receptor activation by extracellular nicotinamide adenine dinucleotide and ecto-ADP-ribosyltransferases in murine macrophages and T cells.
- Authors: Hong S, Schwarz N, Brass A, Seman M, Haag F, Koch-Nolte F, Schilling WP, Dubyak GR
- Issue date: 2009 Jul 1
- NAD+ released during inflammation participates in T cell homeostasis by inducing ART2-mediated death of naive T cells in vivo.
- Authors: Adriouch S, Hubert S, Pechberty S, Koch-Nolte F, Haag F, Seman M
- Issue date: 2007 Jul 1
- NAD induces astrocyte calcium flux and cell death by ART2 and P2X7 pathway.
- Authors: Wang J, Yang J, Liu P, Bi X, Li C, Zhu K
- Issue date: 2012 Sep
- CD38 controls ADP-ribosyltransferase-2-catalyzed ADP-ribosylation of T cell surface proteins.
- Authors: Krebs C, Adriouch S, Braasch F, Koestner W, Leiter EH, Seman M, Lund FE, Oppenheimer N, Haag F, Koch-Nolte F
- Issue date: 2005 Mar 15
- NAD+ and ATP released from injured cells induce P2X7-dependent shedding of CD62L and externalization of phosphatidylserine by murine T cells.
- Authors: Scheuplein F, Schwarz N, Adriouch S, Krebs C, Bannas P, Rissiek B, Seman M, Haag F, Koch-Nolte F
- Issue date: 2009 Mar 1