GrassiScienceSignal2008

GrassiScienceSignal2008 - Purinergic Control of T Cell...

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(39), ra6. [DOI: 10.1126/scisignal.1160583] 1 Science Signaling Grassi (30 September 2008) Marta Fumagalli, Claudia Verderio, Jan Buer, Eugenio Scanziani and Fabio Ursula Schenk, Astrid M. Westendorf, Enrico Radaelli, Anna Casati, Micol Ferro, Pannexin-1 Hemichannels Purinergic Control of T Cell Activation by ATP Released Through This information is current as of 15 October 2008. The following resources related to this article are available online at http://stke.sciencemag.org. Article Tools http://stke.sciencemag.org/cgi/content/full/sigtrans;1/39/ra6 Visit the online version of this article to access the personalization and article tools: Materials Supplemental http://stke.sciencemag.org/cgi/content/full/sigtrans;1/39/ra6/DC1 "Supplementary Materials" References http://stke.sciencemag.org/cgi/content/full/sigtrans;1/39/ra6#otherarticles This article cites 72 articles, 28 of which can be accessed for free: Glossary http://stke.sciencemag.org/glossary/ Look up definitions for abbreviations and terms found in this article: Permissions http://www.sciencemag.org/about/permissions.dtl Obtain information about reproducing this article: the American Association for the Advancement of Science; all rights reserved. by Association for the Advancement of Science, 1200 New York Avenue, NW, Washington, DC 20005. Copyright 2008 (ISSN 1937-9145) is published weekly, except the last week in December, by the American Science Signaling on October 15, 2008 stke.sciencemag.org Downloaded from
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IMMUNOLOGY Purinergic Control of T Cell Activation by ATP Released Through Pannexin-1 Hemichannels Ursula Schenk, 1 Astrid M. Westendorf, 2 Enrico Radaelli, 3 Anna Casati, 1,4 Micol Ferro, 1 Marta Fumagalli, 5 Claudia Verderio, 6 Jan Buer, 2 Eugenio Scanziani, 3 Fabio Grassi 1 * (Published 30 September 2008; Volume 1 Issue 39 ra6) T cell receptor (TCR) stimulation results in the influx of Ca 2+ , 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 develop- ment 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. INTRODUCTION
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GrassiScienceSignal2008 - Purinergic Control of T Cell...

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