Summary
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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| Web resources: | https://cordis.europa.eu/project/id/101165915 |
| Start date: | 01-01-2025 |
| End date: | 31-12-2029 |
| Total budget - Public funding: | 1 499 650,00 Euro - 1 499 650,00 Euro |
Cordis data
Original description
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 immunotherapyStatus
SIGNEDCall topic
ERC-2024-STGUpdate Date
24-11-2024
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