Descrizione del progetto
Svelare il potenziale terapeutico dell’infiammazione guidata dalle cellule T
L’infiammazione è una comune risposta alle lesioni cerebrali acute. Secondo dati raccolti recentemente dal laboratorio ospitante, questa risposta può essere duratura e le cellule T, in base a quanto osservato, vengono dirette dall’intestino mediante la modulazione di batteri commensali, promuovendo intensamente il recupero dall’ictus. Il progetto RecoverInFlame, finanziato dall’UE, sta verificando l’ipotesi secondo cui le cellule T sarebbero inoltre in grado di contribuire al recupero in seguito a lesioni cerebrali attraverso la rimodellizzazione guidata dall’infiammazione. Il team di ricerca approfondirà gli effetti esercitati dalle cellule T sulla connettività corticale e la plasticità della colonna vertebrale, nonché i meccanismi alla base delle risposte gliali. La squadra esaminerà inoltre il contributo apportato dal microbiota intestinale alla risposta neuroinfiammatoria cronica e verificherà le potenzialità traslazionali in modelli di varie lesioni cerebrali acute e patologie associate.
Obiettivo
The overall goal of this project is to investigate T cells as “Trojan horses” to improve recovery from brain injuries – we will gain novel insights on how T cells promote neurologic recovery by modulating the cerebral micromilieu and how these pathomechanisms can be therapeutically targeted.
Inflammation is a common response to acute brain injuries, which are a leading cause of morbidity and mortality. I have recently identified continuous cerebral T cell recruitment as a hallmark of a long-lasting and profound neuroinflammation after acute brain injury. While a detrimental effect of T cells in the acute phase has been well documented, the pathophysiological consequences and therapeutic potential of T cell-driven chronic inflammation for recovery after brain injury are unknown. Interestingly, my recent findings indicate that T cell fate is orchestrated in the gut via modulation of commensal bacteria and that T cells potently promote stroke recovery. Building up on these recent findings, I hypothesize that T cells contribute substantially to the recovery after brain injury by inflammation-driven remodeling. Using several innovative methodologies applied for the first time to recovery after brain injury, we will firstly investigate the contribution of T cells on cortical connectivity, spine plasticity and mechanisms of glial responses. Next, we will analyze the contribution of the gut microbiota to modulate the chronic neuroinflammatory response via a pro-regenerative polarization of T helper cells. Finally, we will test the generalizability and translational robustness of our findings in models of various acute brain injuries and common comorbidities. Results from this project are likely to open up a new research field on T cell-driven neurologic recovery after brain injury, thereby revolutionizing our pathomechanistic understanding and provide novel therapeutic strategies for one of the most pressing medical problems.
Campo scientifico
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
80539 MUNCHEN
Germania