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Immunorégulation par le NAD extracellulaire : activation via les ADP-ribosyl transférases du récepteur cytolytique P2X7

Abstract : Mono ADP-ribosyl transferases (ART) catalyse a posttranslational modification of proteins by transferring the ADP-ribose moiety of NAD to targets proteins. We investigated the functions of this newly identified proteins family and the effects of they substrate, extracellular NAD, on T lymphocytes. Exposure of T cells to micromolar NAD concentrations triggers rapid induction of apoptosis. This phenomenon requires the presence of ART2.2 and of a functional P2X7 ATP receptor. ART2.2-catalysed cell surface protein ADP-ribosylation activates the cytolitic P2X7 purinoreceptor causing pore formation and cell death. Interestingly, much lower NAD than ATP concentration are required to activate P2X7. In vivo, NAD concentration increases in inflamed tissue as a consequence of tissue injury. Based on the results that only peripheral naive T cells are sensitive to NAD, we proposed that NAD would participate to the control of autoimmunty by killing naive T cells surrounding inflamed tissue thereby limiting the activation of bystander T lymphocytes.
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https://tel.archives-ouvertes.fr/tel-00003698
Contributor : Sahil Adriouch <>
Submitted on : Tuesday, November 4, 2003 - 7:09:26 PM
Last modification on : Friday, November 22, 2019 - 9:12:02 AM
Long-term archiving on: : Friday, April 2, 2010 - 6:54:25 PM

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  • HAL Id : tel-00003698, version 1

Citation

Sahil Adriouch. Immunorégulation par le NAD extracellulaire : activation via les ADP-ribosyl transférases du récepteur cytolytique P2X7. Biologie cellulaire. Université Paris-Diderot - Paris VII, 2003. Français. ⟨tel-00003698⟩

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