Project description
T cell-driven autoimmune process leads to chronic brain inflammation with progressive neurodegeneration
The brain is an immune-privileged organ where the resident cells exert limited immune functions. However, in the case of multiple sclerosis, a T cell-induced chronic autoimmune disease, the brain tissue is transformed into an immunoactive milieu. The EU-funded T-Neuron project aims to uncover the mechanisms of T cell-induced neuronal transformation, specifically the functional consequences of T cell invasive behaviour. Previous studies showed that autoaggressive T cells within autoimmune lesions are usually in direct contact with neurons or reside inside the cytoplasm of neurons. The repeated autoimmune attacks of the grey matter induce persistent inflammation and neurodegeneration. The project will test the hypothesis that T cells directly contribute to the development of the chronic disease by irreversibly shifting brain resident cells to an inflammatory state.
Objective
The TOPIC of this proposal is how a T-cell-driven autoimmune process can transform the brain into a chronically inflamed tissue afflicted by progressive neurodegeneration.
The brain is considered to be an immune-privileged organ because immune cells have restricted access to its tissue and its resident cells can only exert limited immune functions. However, in the course of multiple sclerosis, a T-cell-induced chronic autoimmune disease of the brain, such aspects change dramatically and the brain tissue is transformed into an immunoactive milieu. These changes go hand in hand with a gradual degeneration of the neuronal tissue. What steers this transformative process in the brain is not yet understood.
We have developed new experimental models and tools that enable us to follow and functionally test this transition from healthy into degenerating brain tissue in real time. We found that autoaggressive T cells within autoimmune lesions were frequently in direct contact with neurons or were partially or even completely inside the cytoplasm of neurons. Repeated T-cell-mediated autoimmune attacks of the CNS grey matter induce persistent inflammatory lesions with proceeding neurodegeneration. This leads us to the HYPOTHESIS that T cells not only trigger the initiation of autoimmune disease bouts but in addition directly contribute to the chronification of the disease by irreversibly shifting brain resident cells to an inflammatory program. The central AIM of this project is to uncover the mechanisms behind this T-cell-induced neuronal transformation process, particularly the functional consequences of the T-cell invasive behavior.
Our VISION is to shed new light on this previously unknown function of autoaggressive T cells within the CNS tissue and thereby pave the way for new and targeted strategies to prevent autoimmunity-driven degeneration of the central nervous system.
Fields of science
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Funding Scheme
ERC-ADG - Advanced GrantHost institution
37075 Goettingen
Germany