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ATP inhibits the generation and function of regulatory T cells through the activation of purinergic P2X receptors.
Schenk, Ursula Frascoli, Michela Proietti, Michele Geffers, Robert Traggiai, Elisabetta Buer, Jan Ricordi, Camillo Westendorf, Astrid M Grassi, Fabio
Schenk, Ursula
Frascoli, Michela
Proietti, Michele
Geffers, Robert
Traggiai, Elisabetta
Buer, Jan
Ricordi, Camillo
Westendorf, Astrid M
Grassi, Fabio
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Other Titles
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.
Citation
ATP inhibits the generation and function of regulatory T cells through the activation of purinergic P2X receptors. 2011, 4 (162):ra12 Sci Signal
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Journal
PubMed ID
PubMed Central ID
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Article
Language
en
Description
Series/Report no.
ISSN
1937-9145