Description du projet
Découvrir le potentiel thérapeutique de l’inflammation induite par les lymphocytes T
L’inflammation est une réponse courante aux lésions cérébrales aiguës. De récentes données du laboratoire hôte indiquent que cette réponse peut être durable. Il a également été observé que les lymphocytes T sont dirigés depuis l’intestin via la modulation des bactéries commensales, ce qui favorise considérablement la récupération après un accident vasculaire cérébral. Le projet RecoverInFlame, financé par l’UE, explore l’hypothèse selon laquelle les lymphocytes T peuvent également contribuer à la récupération après une lésion cérébrale par le biais d’un remodelage induit par l’inflammation. L’équipe de recherche étudiera les effets des lymphocytes T sur la connectivité corticale et la plasticité de la colonne vertébrale, ainsi que les mécanismes des réponses gliales. Elle étudiera également la contribution du microbiote intestinal à la réponse neuro-inflammatoire chronique et testera les possibilités de transfert dans des modèles de diverses lésions cérébrales aiguës et de comorbidités.
Objectif
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.
Champ scientifique
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ERC-STG - Starting GrantInstitution d’accueil
80539 MUNCHEN
Allemagne