Purinergic Control of T Cell Activation by ATP Released Through Pannexin-1 Hemichannels

Sci. Signal., 30 September 2008
Vol. 1, Issue 39, p. ra6
DOI: 10.1126/scisignal.1160583

Purinergic Control of T Cell Activation by ATP Released Through Pannexin-1 Hemichannels

  1. Ursula Schenk1,
  2. Astrid M. Westendorf2,
  3. Enrico Radaelli3,
  4. Anna Casati1,4,
  5. Micol Ferro1,
  6. Marta Fumagalli5,
  7. Claudia Verderio6,
  8. Jan Buer2,
  9. Eugenio Scanziani3, and
  10. Fabio Grassi1,*
  1. 1Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland.
  2. 2Institute of Medical Microbiology, University Hospital Essen, 45122 Essen, Germany.
  3. 3Department of Veterinary Pathology, Hygiene and Public Health, University of Milan, 20100 Milan, Italy.
  4. 4Department of Biology and Genetics for Medical Sciences, University of Milan, 20100 Milan, Italy.
  5. 5Department of Pharmacological Sciences, University of Milan, 20100 Milan, Italy.
  6. 6Department of Medical Pharmacology, CNR Institute of Neuroscience, University of Milan, 20100 Milan, Italy.
  1. *To whom correspondence should be addressed. E-mail: fabio.grassi{at}irb.unisi.ch

Abstract

T cell receptor (TCR) stimulation results in the influx of Ca2+, which is buffered by mitochondria and promotes adenosine triphosphate (ATP) synthesis. We found that ATP released from activated T cells through pannexin-1 hemichannels activated purinergic P2X receptors (P2XRs) to sustain mitogen-activated protein kinase (MAPK) signaling. P2XR antagonists, such as oxidized ATP (oATP), blunted MAPK activation in stimulated T cells, but did not affect the nuclear translocation of the transcription factor nuclear factor of activated T cells, thus promoting T cell anergy. In vivo administration of oATP blocked the onset of diabetes mediated by anti-islet TCR transgenic T cells and impaired the development of colitogenic T cells in inflammatory bowel disease. Thus, pharmacological inhibition of ATP release and signaling could be beneficial in treating T cell–mediated inflammatory diseases.

Citation:

U. Schenk, A. M. Westendorf, E. Radaelli, A. Casati, M. Ferro, M. Fumagalli, C. Verderio, J. Buer, E. Scanziani, and F. Grassi, Purinergic Control of T Cell Activation by ATP Released Through Pannexin-1 Hemichannels. Sci. Signal. 1, ra6 (2008).

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Both sides now: multiple interactions of ATP with pannexin-1 hemichannels. Focus on "A permeant regulating its permeation pore: inhibition of pannexin 1 channels by ATP"
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