Objectif It is estimated that more than 200 million Europeans suffer from at least one type of allergy. This condition is elicited by an hyper-activated type-2 inflammatory response coordinated by T helper (TH)-2 cells. In spite a good insight into the molecular mechanisms that triggers TH2 cells activation, the lack in understanding their post-transcriptional regulation is hampering the access to new potential therapeutic targets to curtail the allergy epidemic.Micro-RNA (miRNAs) are regulatory molecules essential for life, which play a fundamental role in shaping cellular functions via post-transcriptional repression of the cellular transcriptome. Though previously considered to operate exclusively inside the parent cell, it is now acknowledged that miRNAs can exit cellular boundaries and control transcription in bystander cells. We recently reported that regulatory T (TREG) cells secret specific miRNAs to repress TH1 cell-mediated immunopathology, and ameliorate a mouse model of autoimmune disease.In this proposal, we will address the role of extracellular miRNAs for the normal T cell development and during allergic inflammation of the airways. To this end, we produced a novel animal model that allows - for the first time - to selectively ablate the activity of extracellular miRNAs in T cells. We will use biochemical, RNA-sequencing and bioinformatics analysis to identify the molecular mechanisms for miRNAs sorting to exocytosis and to identify the miRNAs transferred to and from TH2 cells. This proposal will significantly expand our understanding of transferred miRNAs in the contest of health and disease, and will uncover novel cellular pathways to exploit as therapeutic targets. Champ scientifique medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverymedical and health sciencesclinical medicinepneumologyasthmamedical and health sciencesbasic medicineimmunologyautoimmune diseasesmedical and health sciencesbasic medicinepathologymedical and health sciencesclinical medicineallergology Mots‑clés extracellular miRNAs T cell development Allergy Helminth infection Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Thème(s) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Appel à propositions H2020-MSCA-IF-2014 Voir d’autres projets de cet appel Régime de financement MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinateur THE FRANCIS CRICK INSTITUTE LIMITED Contribution nette de l'UE € 183 454,80 Adresse 1 MIDLAND ROAD NW1 1AT London Royaume-Uni Voir sur la carte Région London Inner London — West Camden and City of London Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 183 454,80 Participants (1) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire UNITED KINGDOM RESEARCH AND INNOVATION Participation terminée Royaume-Uni Contribution nette de l'UE € 0,00 Adresse POLARIS HOUSE NORTH STAR AVENUE SN2 1FL Swindon Voir sur la carte Région South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Swindon Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total Aucune donnée