Abstracts
Résumé
La tyrosine kinase ZAP-70 (zeta-chain-associated protein of 70 kDa) a connu son heure de gloire au début des années 1990, lorsque des mutations du gène codant pour cette protéine ont été mises en évidence chez de très jeunes patients présentant des déficits immunitaires combinés sévères. La caractérisation, chez ces patients, de déficits fonctionnels des lymphocytes T signait le rôle crucial de cette protéine dans l’activation de ces cellules. Très récemment, un regain d’intérêt pour ZAP-70 est apparu lorsque son expression, dans un premier temps considérée comme spécifique des lymphocytes T et des cellules NK (natural killer), a été mise en évidence dans certaines leucémies lymphoïdes chroniques B et associée à un facteur pronostique. Enfin, la découverte d’une mutation ponctuelle spontanée de ZAP-70 dans une souche de souris présentant une arthrite rhumatoïde révélait également le rôle potentiel de ZAP-70 dans des maladies auto-immunes. Les diverses maladies associées à des modifications d’expression ou d’activité de ZAP-70 démontrent le rôle clé de cette kinase dans la mise en place et la régulation d’une réponse immunitaire.
Summary
The ZAP-70 tyrosine kinase has been described more than ten years ago. Its key role in thymocytes development and mature T lymphocytes activation has been illustrated by the characterization of several human immunodeficiencies presenting with mutations in the zap-70 gene resulting in the absence of ZAP-70 expression. More recently, it has been shown that deregulation of ZAP-70 activity can induce autoimmune diseases. Finally, ZAP-70 expression has been shown in some B chronic lymphocytic leukaemia and correlated with bad prognosis of the disease. The diversity of pathologies associated with deregulation of ZAP-70 demonstrates its key role in immune responses. Research aiming at deciphering the different signalling pathways regulated by ZAP-70 will not only shed some lights on these pathologies, but will also help finding new pharmacological tools, targeting ZAP-70, designed to induce immunosuppression or tolerance.
Appendices
Références
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