http://hdl.handle.net/10033/128110 Arbeitsgruppenleiter: Prof.Dr. J.Hühn Fri, 24 May 2013 12:34:17 GMT 2013-05-24T12:34:17Z http://hdl.handle.net/10033/132850 Title: Extracellular NAD+ shapes the Foxp3+ regulatory T cell compartment through the ART2-P2X7 pathway. Authors: Hubert, Sandra; Rissiek, Björn; Klages, Katjana; Huehn, Jochen; Sparwasser, Tim; Haag, Friedrich; Koch-Nolte, Friedrich; Boyer, Olivier; Seman, Michel; Adriouch, Sahil Abstract: CD4(+)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. Mon, 22 Nov 2010 00:00:00 GMT http://hdl.handle.net/10033/132850 2010-11-22T00:00:00Z http://hdl.handle.net/10033/128113 Title: To be or not to be a Treg cell: lineage decisions controlled by epigenetic mechanisms. Authors: Toker, Aras; Huehn, Jochen Abstract: Regulatory T (T(reg)) cells are a unique CD4(+) T cell lineage that plays a crucial role in the maintenance of immunological tolerance. The Forkhead box transcription factor Foxp3 is critically involved in T(reg) cell development and responsible for determining the suppressive function of these cells. The majority of Foxp3(+) T(reg) cells are generated during T cell development within the thymus and show features of a stable T cell lineage. New work indicates that both induction and stabilization of Foxp3 expression are under epigenetic control, which suggests that selective interference with the underlying chromatin remodeling mechanisms might enable the development of future therapeutic strategies targeting T(reg) cells. Sat, 01 Jan 2011 00:00:00 GMT http://hdl.handle.net/10033/128113 2011-01-01T00:00:00Z