Descrizione del progetto
Cambiamenti legati all’età nel microambiente dei linfociti T
L’invecchiamento è associato a cambiamenti nei processi biologici e fisiologici in tutto l’organismo. Inoltre, influisce sulla funzione del sistema immunitario, compresi i linfociti T. Finanziato dal Consiglio europeo della ricerca, il progetto IMMAGE si propone di studiare l’impatto dell’invecchiamento sul microambiente dei linfociti T e se questo sia responsabile della disfunzione dei linfociti T legata all’età. I ricercatori si concentreranno sull’eventualità che un microambiente invecchiato non riesca a fornire un adeguato supporto metabolico ai linfociti T o rilasci segnali tossici che inibiscono il metabolismo dei linfociti T. Oltre alle conoscenze fondamentali, i risultati del progetto prepareranno il terreno a strategie di ringiovanimento dell’immunità dei linfociti T.
Obiettivo
T lymphocytes play a central role in the immune defense against intruders, and support tissue homeostasis and function. Strikingly, an aged or dysfunctional T cell immunity is sufficient to promote organ aging and multiple age-related morbidities. In this proposal we hypothesize that there is a bidirectional relationship between T cells and their in vivo microenvironment that could develop into a vicious cycle under conditions of aging and disease. While a lot is known about the cellular mechanisms underlying T cell dysfunction with age, A profound understanding of how aging of the microenvironment impacts T cell immunity is missing. This work directly targets this gap to determine how the in vivo microenvironment in an aged mouse dictates T cells aging trajectories. Following on our preliminary findings, we will study two major mechanisms: (1) deficient metabolic support: we propose novel mechanisms by which stromal cells in the T cell zone of secondary lymphoid organs provide T cells metabolic needs for activation, and its failure in aged lymph nodes; and (2) toxic signals specific to the aged spleen that inhibit T cell metabolism and activation. Finally, we will investigate whether targeting these pathways would rejuvenate T cell immunity in vivo. The proposed study will discover unknown mechanisms supporting T cells metabolism in situ and will provide a causative link between T cell aging phenotypes and aging of their microenvironment. Finding new ways to rejuvenate immunity holds the promise for comprehensive and simultaneous targeting of multiple age-related pathologies.
Campo scientifico
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
ERC - Support for frontier research (ERC)Istituzione ospitante
32000 Haifa
Israele