TY - JOUR
T1 - Purinergic control of T cell activation by ATP released through pannexin-1 hemichannels
AU - Schenk, Ursula
AU - Westendorf, Astrid M.
AU - Radaelli, Enrico
AU - Casati, Anna
AU - Ferro, Micol
AU - Fumagalli, Marta
AU - Verderio, Claudia
AU - Buer, Jan
AU - Scanziani, Eugenio
AU - Grassi, Fabio
PY - 2008/9/30
Y1 - 2008/9/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=55649113607&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=55649113607&partnerID=8YFLogxK
U2 - 10.1126/scisignal.1160583
DO - 10.1126/scisignal.1160583
M3 - Article
C2 - 18827222
AN - SCOPUS:55649113607
VL - 1
JO - Science Signaling
JF - Science Signaling
SN - 1937-9145
IS - 39
M1 - ra6
ER -