Descrizione del progetto
Il ruolo delle cellule T mucosali nella riparazione dei tessuti
Le cellule T invarianti associate alla mucosa (MAIT) sono un gruppo specializzato di cellule T che riconoscono specifici ligandi nei tessuti mucosali. È interessante notare che queste cellule si differenziano nel timo durante lo sviluppo tramite meccanismi sconosciuti. Gli scienziati del progetto MAIT, finanziato dall’UE, studieranno il modo in cui i tessuti e i segnali ambientali guidano questa differenziazione timica e determinano la funzione delle cellule MAIT. Concentreranno l’attenzione sul ruolo effettore e protettivo delle cellule MAIT nella guarigione delle ferite cutanee e dell’infezione da influenza. Oltre a fornire informazioni fondamentali su questa popolazione di cellule T, i risultati porranno le basi per l’utilizzo delle cellule MAIT nella stimolazione della riparazione dei tessuti.
Obiettivo
Mucosal associated invariant T cells (MAITs) represent an abundant subset in humans with unique specificity for microbial metabolites. MAIT conservation along evolution indicates important, non-redundant functions. Despite changes in MAIT frequency and phenotype in several infectious and non-infectious diseases, their functions are still unclear. By contrast with mainstream CD4+ or CD8+ T cells, MAITs differentiate into effector cells during thymic development. How the differentiation program imparted in the thymus is modified by tissue and environmental cues to determine MAIT functions in tissues is not known. Our preliminary data support a new function for MAITs in boosting tissue repair in skin wound healing and flu infection. Thus, MAITs would either repair tissues or inflict tissue damage when fighting microbes according to the stage of the disease. To understand how and when the different MAIT functions are turned on and off in vivo we will study: 1) How is the thymic MAIT differentiation program modulated by tissue and environmental cues to determine the location and effector functions of MAITs in skin and lung at steady state? To this end we will develop new genetic methods to modify MAIT development or functions. 2) What are the effector functions of MAITs leading to protection during skin wound healing and flu infection? We will determine the cell types MAITs affect and identify the mediators secreted by MAIT cells. 3) What triggers MAIT protective effect? We will identify the drivers of MAIT activation and assess the requirement for cognate or non-cognate (cytokines) interactions. Wound healing of human skin explants will test the therapeutic potential of modulating MAIT activation. Our results will provide unique insight on the functions of MAIT cells with important implications for therapy of diseases in which MAIT triggering (or inhibition) could be beneficial (or deleterious) such as wounds or infections that damage tissues and thus require repair.
Campo scientifico
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-ADG - Advanced GrantIstituzione ospitante
75231 Paris
Francia