Project description
Uncovering the therapeutic potential of T cell-driven inflammation
Inflammation is a common response to acute brain injuries. Recent data from the host lab indicated that this response can be long-lasting; it was also observed that T cells are directed from the gut via modulation of commensal bacteria, potently promoting stroke recovery. The EU-funded RecoverInFlame project is exploring the hypothesis that T cells can also contribute to recovery after brain injury via inflammation-driven remodelling. The research team will investigate the effects of T cells on cortical connectivity and spine plasticity as well as the mechanisms of glial responses. They will also study the contribution of the gut microbiota to the chronic neuroinflammatory response and test the translational potentials in models of various acute brain injuries and comorbidities.
Objective
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.
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Funding Scheme
ERC-STG - Starting GrantHost institution
80539 MUNCHEN
Germany