Description du projet
Changements liés à l'âge dans le microenvironnement des lymphocytes T
Le vieillissement est associé à des changements au niveau des processus biologiques et physiologiques de tout l’organisme. Il nuit également au fonctionnement du système immunitaire, y compris des lymphocytes T. Financé par le Conseil européen de la recherche, le projet IMMAGE vise à étudier l’incidence du vieillissement sur le microenvironnement des lymphocytes T et à déterminer s’il est responsable du dysfonctionnement des lymphocytes T lié à l’âge. Les chercheurs se concentreront sur la possibilité qu’un microenvironnement âgé ne parvient pas à apporter un soutien métabolique adéquat aux lymphocytes T ou libère des signaux toxiques qui inhibent le métabolisme de ces derniers. En plus de produire des connaissances fondamentales, les résultats du projet ouvriront la voie à des stratégies de régénération de l’immunité des lymphocytes T.
Objectif
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.
Champ scientifique
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thème(s)
Régime de financement
ERC - Support for frontier research (ERC)Institution d’accueil
32000 Haifa
Israël