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Immune mechanisms of experience induced brain plasticity: the contribution of brain resident T cells

Objective

T cells are part of the adaptive immune response. Breaking the dogma of the brain immune privilege I demonstrated the presence of T cells in the healthy brain. In the mouse brain they regulate neuronal morphology and behavior. Surprisingly, brain T cells respond and proliferate upon exposure to an enriched environment (EE), suggesting a connection between neural activity and brain T cells. EE involves motoric, sensory and social stimulation. Exposure of rodents to EE increases neurogenesis, enhances learning and memory, with proven beneficial effect in neuropathology. How brain T cells can respond to EE and eventually modify the brain is unknown. I hypothesize that upon EE, T cells adapt their molecular profile and acquire an immunomodulatory phenotype to support the changes occurring in the brain. My overarching goal is to understand how EE modulates immune-brain interactions and to harness emerging discoveries to develop novel therapeutic interventions for neurodevelopmental disorders, that mimic the beneficial effects of EE. Currently, research into brain functions of T cells is limited by absence of research tools to deplete T cells in the brain only. The proposed project will overcome these limitations by developing a novel gene therapy approach for depleting brain T cells . First, I will investigate how EE influences brain immunity. Then I will take the opposite approach, investigating whether and how brain immune cells act as a necessary mediator of EE-induced brain plasticity, making use of the new nanobody-based tool to deplete brain T cells. These complementary approaches will allow me to mechanistically decipher how experience influences interactions between the brain and the immune system. Finally, using the Fragile X mouse model of Autism, I will translate the knowledge gained from brain resident T cells into impactful proof-of-concepts for treating neurological diseases and mimicking the benefits of environmental enrichment through immunotherapy

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2024-STG

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Host institution

VIB VZW
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 499 650,00
Address
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Belgium

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Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 499 650,00

Beneficiaries (1)

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