ATP inhibits the generation and function of regulatory T cells through the activation of purinergic P2X receptors.
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Westendorf, Astrid M
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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.
CitationATP inhibits the generation and function of regulatory T cells through the activation of purinergic P2X receptors. 2011, 4 (162):ra12 Sci Signal
AffiliationInstitute for Research in Biomedicine, Bellinzona, Switzerland.
The following license files are associated with this item:
- Extracellular ATP exerts opposite effects on activated and regulatory CD4+ T cells via purinergic P2 receptor activation.
- Authors: Trabanelli S, Ocadlíková D, Gulinelli S, Curti A, Salvestrini V, Vieira RP, Idzko M, Di Virgilio F, Ferrari D, Lemoli RM
- Issue date: 2012 Aug 1
- Autocrine regulation of T-cell activation by ATP release and P2X7 receptors.
- Authors: Yip L, Woehrle T, Corriden R, Hirsh M, Chen Y, Inoue Y, Ferrari V, Insel PA, Junger WG
- Issue date: 2009 Jun
- Purinergic P2X7 receptor drives T cell lineage choice and shapes peripheral γδ cells.
- Authors: Frascoli M, Marcandalli J, Schenk U, Grassi F
- Issue date: 2012 Jul 1
- ATP induces P2X7 receptor-independent cytokine and chemokine expression through P2X1 and P2X3 receptors in murine mast cells.
- Authors: Bulanova E, Budagian V, Orinska Z, Koch-Nolte F, Haag F, Bulfone-Paus S
- Issue date: 2009 Apr
- Shockwaves increase T-cell proliferation and IL-2 expression through ATP release, P2X7 receptors, and FAK activation.
- Authors: Yu T, Junger WG, Yuan C, Jin A, Zhao Y, Zheng X, Zeng Y, Liu J
- Issue date: 2010 Mar