ATP inhibits the generation and function of regulatory T cells through the activation of purinergic P2X receptors.

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Hdl Handle:
http://hdl.handle.net/10033/141792
Title:
ATP inhibits the generation and function of regulatory T cells through the activation of purinergic P2X receptors.
Authors:
Schenk, Ursula; Frascoli, Michela; Proietti, Michele; Geffers, Robert; Traggiai, Elisabetta; Buer, Jan; Ricordi, Camillo; Westendorf, Astrid M; Grassi, Fabio
Abstract:
Extracellular 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.
Affiliation:
Institute for Research in Biomedicine, Bellinzona, Switzerland.
Citation:
ATP inhibits the generation and function of regulatory T cells through the activation of purinergic P2X receptors. 2011, 4 (162):ra12 Sci Signal
Journal:
Science signaling
Issue Date:
2011
URI:
http://hdl.handle.net/10033/141792
DOI:
10.1126/scisignal.2001270
PubMed ID:
21364186
Type:
Article
Language:
en
ISSN:
1937-9145
Appears in Collections:
publications of the research group genomeanalytics (GMAK)

Full metadata record

DC FieldValue Language
dc.contributor.authorSchenk, Ursulaen
dc.contributor.authorFrascoli, Michelaen
dc.contributor.authorProietti, Micheleen
dc.contributor.authorGeffers, Roberten
dc.contributor.authorTraggiai, Elisabettaen
dc.contributor.authorBuer, Janen
dc.contributor.authorRicordi, Camilloen
dc.contributor.authorWestendorf, Astrid Men
dc.contributor.authorGrassi, Fabioen
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.en
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

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