Purinergic control of T cell activation by ATP released through pannexin-1 hemichannels

Ursula Schenk, Astrid M. Westendorf, Enrico Radaelli, Anna Casati, Micol Ferro, Marta Fumagalli, Claudia Verderio, Jan Buer, Eugenio Scanziani, Fabio Grassi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article numberra6
JournalScience Signaling
Volume1
Issue number39
DOIs
Publication statusPublished - Sep 30 2008

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ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Schenk, U., Westendorf, A. M., Radaelli, E., Casati, A., Ferro, M., Fumagalli, M., Verderio, C., Buer, J., Scanziani, E., & Grassi, F. (2008). Purinergic control of T cell activation by ATP released through pannexin-1 hemichannels. Science Signaling, 1(39), [ra6]. https://doi.org/10.1126/scisignal.1160583