Descripción del proyecto
Cambios relacionados con la edad en el microentorno de los linfocitos T
El envejecimiento se asocia con cambios en los procesos biológicos y fisiológicos de todo el organismo. También afecta al funcionamiento del sistema inmunitario, incluidos los linfocitos T. El equipo del proyecto IMMAGE, financiado por el Consejo Europeo de Investigación, aspira a investigar los efectos del envejecimiento en el microentorno de los linfocitos T y comprobar si es responsable de la disfunción de los linfocitos T relacionada con la edad. Los investigadores se centrarán en la posibilidad de que un microentorno envejecido deje de proporcionar el soporte metabólico adecuado para los linfocitos T o libere señales tóxicas que inhiban el metabolismo de los linfocitos T. Además de aportar conocimientos fundamentales, los resultados del proyecto allanarán el camino hacia estrategias de rejuvenecimiento para la inmunidad de los linfocitos T.
Objetivo
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.
Ámbito científico
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
ERC - Support for frontier research (ERC)Institución de acogida
32000 Haifa
Israel