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Sci. Signal., 30 September 2008 RESEARCHPurinergic Control of T Cell Activation by ATP Released Through Pannexin-1 HemichannelsUrsula Schenk1, Astrid M. Westendorf2, Enrico Radaelli3, Anna Casati1,4, Micol Ferro1, Marta Fumagalli5, Claudia Verderio6, Jan Buer2, Eugenio Scanziani3, and Fabio Grassi1*
1 Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland. 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. * To whom correspondence should be addressed. E-mail: fabio.grassi{at}irb.unisi.ch
Citation: U. Schenk, A. M. Westendorf, E. Radaelli, A. Casati, M. Ferro, M. Fumagalli, C. Verderio, J. Buer, E. Scanziani, F. Grassi, Purinergic Control of T Cell Activation by ATP Released Through Pannexin-1 Hemichannels. Sci. Signal. 1, ra6 (2008). The editors suggest the following Related Resources on Science sites:In Science Signaling
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Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882