Obiettivo MicroRNAs (miRNAs) can be transferred between cells, representing an exciting new dimension to intercellular communication, referred to as non-cell-autonomous gene regulation. We recently identified that distinct miRNAs are packaged and exported from TREG cells and delivered directly to TH1 cells, suppressing T cell-mediated disease. Different T cell populations express different miRNAs and release a distinctive set of extracellular miRNAs. In this proposal we will identify whether the transfer of miRNAs between cells contributes to T cell development, T cell differentiation and TH2-mediated allergy and anti-helminth immunity. miRNA-mediated gene silencing requires one of four catalytically active Argonaut (Ago) proteins to regulate gene expression. To investigate miRNA transport between cells, we have generated novel mice with miRNA-deficient T cells that can (Dicer–/–) or cannot (Dicer–/–Ago-1,-3,-4–/– Ago-2fl/fl) respond to exogenous miRNAs. Using these novel mice we will identify which Ago protein(s) specific miRNAs associate with and which Ago proteins are required for miRNA-mediated gene regulation in T cells. TH2 cells express unique miRNAs, which can be found within TH2 cells and in extracellular vesicles released from TH2 cells. We have generated several new TH2-associated miRNA-deficient mice to investigate the cell intrinsic (cell-autonomous) and extrinsic (non-cell-autonomous) role of these miRNAs in TH2-mediated allergy and anti-helminth immunity. Studies in plants and worms have identified various mechanisms of RNA transfer between cells, involving cell-contact dependent and independent mechanisms. We will translate these observations into mammalian systems and identify the mechanisms of miRNA transfer. Results from this work will identify novel miRNA-mediated pathways and incentivise state-of-the-art approaches for novel therapeutic intervention to treat inflammatory diseases. Campo scientifico medical and health scienceshealth sciencesinflammatory diseasesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencescell biologymedical and health sciencesclinical medicineallergologynatural sciencesbiological sciencesgeneticsRNA Parole chiave micro RNA (miRNA) T lymphocyte Type-2 immunity Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-CoG-2014 - ERC Consolidator Grant Invito a presentare proposte ERC-2014-CoG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-COG - Consolidator Grant Istituzione ospitante THE FRANCIS CRICK INSTITUTE LIMITED Contribution nette de l'UE € 1 762 510,00 Indirizzo 1 MIDLAND ROAD NW1 1AT London Regno Unito Mostra sulla mappa Regione London Inner London — West Camden and City of London Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 762 510,00 Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto THE FRANCIS CRICK INSTITUTE LIMITED Regno Unito Contribution nette de l'UE € 1 762 510,00 Indirizzo 1 MIDLAND ROAD NW1 1AT London Mostra sulla mappa Regione London Inner London — West Camden and City of London Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 762 510,00