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dc.contributor.authorSchenk, Ursula
dc.contributor.authorFrascoli, Michela
dc.contributor.authorProietti, Michele
dc.contributor.authorGeffers, Robert
dc.contributor.authorTraggiai, Elisabetta
dc.contributor.authorBuer, Jan
dc.contributor.authorRicordi, Camillo
dc.contributor.authorWestendorf, Astrid M
dc.contributor.authorGrassi, Fabio
dc.date.accessioned2011-09-06T11:25:54Z
dc.date.available2011-09-06T11:25:54Z
dc.date.issued2011
dc.identifier.citationATP inhibits the generation and function of regulatory T cells through the activation of purinergic P2X receptors. 2011, 4 (162):ra12 Sci Signalen
dc.identifier.issn1937-9145
dc.identifier.pmid21364186
dc.identifier.doi10.1126/scisignal.2001270
dc.identifier.urihttp://hdl.handle.net/10033/141792
dc.description.abstractExtracellular nucleotides are pleiotropic regulators of mammalian cell function. Adenosine triphosphate (ATP) released from CD4(+) helper T cells upon stimulation of the T cell receptor (TCR) contributes in an autocrine manner to the activation of mitogen-activated protein kinase (MAPK) signaling through purinergic P2X receptors. Increased expression of p2rx7, which encodes the purinergic receptor P2X7, is part of the transcriptional signature of immunosuppressive CD4(+)CD25(+) regulatory T cells (T(regs)). Here, we show that the activation of P2X7 by ATP inhibits the suppressive potential and stability of T(regs). The inflammatory cytokine interleukin-6 (IL-6) increased ATP synthesis and P2X7-mediated signaling in T(regs), which induced their conversion to IL-17-secreting T helper 17 (T(H)17) effector cells in vivo. Moreover, pharmacological antagonism of P2X receptors promoted the cell-autonomous conversion of naïve CD4(+) T cells into T(regs) after TCR stimulation. Thus, ATP acts as an autocrine factor that integrates stimuli from the microenvironment and cellular energetics to tune the developmental and immunosuppressive program of the T cell in adaptive immune responses.
dc.language.isoenen
dc.subject.meshAdenosine Triphosphateen
dc.subject.meshHumansen
dc.subject.meshReceptors, Purinergic P2en
dc.subject.meshT-Lymphocytes, Regulatoryen
dc.titleATP inhibits the generation and function of regulatory T cells through the activation of purinergic P2X receptors.en
dc.typeArticleen
dc.contributor.departmentInstitute for Research in Biomedicine, Bellinzona, Switzerland.en
dc.identifier.journalScience signalingen
refterms.dateFOA2018-06-13T21:38:48Z
html.description.abstractExtracellular nucleotides are pleiotropic regulators of mammalian cell function. Adenosine triphosphate (ATP) released from CD4(+) helper T cells upon stimulation of the T cell receptor (TCR) contributes in an autocrine manner to the activation of mitogen-activated protein kinase (MAPK) signaling through purinergic P2X receptors. Increased expression of p2rx7, which encodes the purinergic receptor P2X7, is part of the transcriptional signature of immunosuppressive CD4(+)CD25(+) regulatory T cells (T(regs)). Here, we show that the activation of P2X7 by ATP inhibits the suppressive potential and stability of T(regs). The inflammatory cytokine interleukin-6 (IL-6) increased ATP synthesis and P2X7-mediated signaling in T(regs), which induced their conversion to IL-17-secreting T helper 17 (T(H)17) effector cells in vivo. Moreover, pharmacological antagonism of P2X receptors promoted the cell-autonomous conversion of naïve CD4(+) T cells into T(regs) after TCR stimulation. Thus, ATP acts as an autocrine factor that integrates stimuli from the microenvironment and cellular energetics to tune the developmental and immunosuppressive program of the T cell in adaptive immune responses.


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