Objectif Inflammatory diseases affect over 80 million people worldwide and accompany many diseases of industrialized countries, being the majority of them infection-free conditions. There are few efficient anti-inflammatory drugs to treat chronic inflammation and thus, there is an urgent need to validate novel targets. We now know that innate immunity is the main coordinator and driver of inflammation. Recently, we and others have shown that the activation of purinergic P2X7 receptors (P2X7R) in immune cells is a novel and increasingly validated pathway to initiate inflammation through the activation of the NLRP3 inflammasome and the release of IL-1β and IL-18 cytokines. However, how NLRP3 sense P2X7R activation is not fully understood. Furthermore, extracellular ATP, the physiological P2X7R agonist, is a crucial danger signal released by injured cells, and one of the most important mediators of infection-free inflammation. We have also identified novel signalling roles for P2X7R independent on the NLRP3 inflammasome, including the release of proteases or inflammatory lipids. Therefore, P2X7R has generated increasing interest as a therapeutic target in inflammatory diseases, being drug like P2X7R antagonist in clinical trials to treat inflammatory diseases. However, it is often questioned the functionality of P2X7R in vivo, where it is thought that extracellular ATP levels are below the threshold to activate P2X7R. The overall significance of this proposal relays to elucidate how extracellular ATP controls host-defence in vivo, ultimately depicting P2X7R signalling through and beyond inflammasome activation. We foresee that our results will generate a leading innovative knowledge about in vivo extracellular ATP signalling during the host response to infection and sterile danger. Champ scientifique medical and health scienceshealth sciencesinflammatory diseasesmedical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesbiochemistrybiomoleculeslipids Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-CG-2013-LS6 - ERC Consolidator Grant - Immunity and Infection Appel à propositions ERC-2013-CoG Voir d’autres projets de cet appel Régime de financement ERC-CG - ERC Consolidator Grants Institution d’accueil FUNDACION PARA LA FORMACION E INVESTIGACION SANITARIAS DE LA REGION DE MURCIA Contribution de l’UE € 1 794 948,00 Adresse CALLE CAMPO 12 PABELLON DOCENTE DEL HOSPITAL CLINICO UNIVERSITARIO VIRGEN DE LA ARRIXACA 3 PLANTA EL PALMA 30120 Murcia Espagne Voir sur la carte Région Sur Región de Murcia Murcia Type d’activité Research Organisations Contact administratif Juan Pedro Serna Marmol (Mr.) Chercheur principal Pablo Pelegrin Vivancos (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire FUNDACION PARA LA FORMACION E INVESTIGACION SANITARIAS DE LA REGION DE MURCIA Espagne Contribution de l’UE € 1 794 948,00 Adresse CALLE CAMPO 12 PABELLON DOCENTE DEL HOSPITAL CLINICO UNIVERSITARIO VIRGEN DE LA ARRIXACA 3 PLANTA EL PALMA 30120 Murcia Voir sur la carte Région Sur Región de Murcia Murcia Type d’activité Research Organisations Contact administratif Juan Pedro Serna Marmol (Mr.) Chercheur principal Pablo Pelegrin Vivancos (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée