Objective Background: CD4+ T lymphocyte subsets orchestrate immune responses in health and disease. Little is known on control of T cell differentiation exerted by microRNA that affect mRNA translation. The identification of microRNA and their targets that regulate differentiation of T cell subsets may provide new therapeutic targets for immune-mediated diseases. Since microRNA are released in exosomes and circulate in blood, activities of tissue-derived lymphocytes could be assessed by microRNA signatures in the serum. We have defined microRNAs present in resting lymphocyte subsets from peripheral blood and measured lymphocyte-derived microRNAs in the serum. We have also solved important challenges for the identification of microRNA targets, the definition of signatures of activated T cells and their monitoring in the serum, which form the key topics of this application. Advancing State-of-the-Art and objectives: We will identify microRNA of CD4+ T cell subsets purified from inflamed organs and investigate microRNA target network that regulates T cell differentiation. We will exploit this knowledge to profile signatures of in vivo activated T cells and to map genes that could improve understanding of T cell commitment. We will also develop quantitative assays to monitor microRNA signatures in the serum and provide functional evidence of key genes targeted by microRNA which could be targets of immunomodulatory drugs. Significance: This application addresses important challenges at the frontiers of immunology and could lead to significant advances in immunotherapies and diagnostic tools for patients with immune mediated diseases. New ways of identifying microRNA targets and techniques to quantify microRNA signatures in the serum, could be widely applicable in biomedical research. Fields of science natural sciencesbiological sciencescell biologymedical and health sciencesbasic medicineimmunologyimmunotherapy 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) Topic(s) ERC-AG-LS7 - ERC Advanced Grant - Diagnostic tools, therapies and public health Call for proposal ERC-2010-AdG_20100317 See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Coordinator UNIVERSITA DEGLI STUDI DI MILANO Address Via festa del perdono 7 20122 Milano Italy See on map Region Nord-Ovest Lombardia Milano Activity type Higher or Secondary Education Establishments Administrative Contact Gerardo D'errico (Mr.) Principal investigator Sergio Abrignani (Prof.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution € 30 120,00 Beneficiaries (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSITA DEGLI STUDI DI MILANO Italy EU contribution € 30 120,00 Address Via festa del perdono 7 20122 Milano See on map Region Nord-Ovest Lombardia Milano Activity type Higher or Secondary Education Establishments Administrative Contact Gerardo D'errico (Mr.) Principal investigator Sergio Abrignani (Prof.) Links Contact the organisation Opens in new window Website Opens in new window FONDAZIONE ISTITUTO NAZIONALE DI GENETICA MOLECOLARE INGM Italy EU contribution € 2 465 880,00 Address Via francesco sforza 35 20122 Milano See on map Region Nord-Ovest Lombardia Milano Activity type Research Organisations Administrative Contact Stefano Apollonio (Mr.) Links Contact the organisation Opens in new window Website Opens in new window
