T-cell-induced immune programming and degeneration of the neuronal tissue during chronic autoimmunity

Project Information

T-Neuron

Grant agreement ID: 101021345

DOI

10.3030/101021345

EC signature date 10 July 2021

Start date 1 September 2021

End date 31 August 2027

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 2 374 863,00

EU contribution

€ 2 374 863,00

Coordinated by

UNIVERSITAETSMEDIZIN GOETTINGEN - GEORG-AUGUST-UNIVERSITAET GOETTINGEN - STIFTUNG OEFFENTLICHEN RECHTS
Germany

Periodic Reporting for period 3 - T-Neuron (T-cell-induced immune programming and degeneration of the neuronal tissue during chronic autoimmunity)

Reporting period: 2024-09-01 to 2026-02-28

Summary of the context and overall objectives of the project

The project investigates why multiple sclerosis, an autoimmune disease of the central nervous system, takes a chronic, progressive course. In particular, we are investigating which immune processes are responsible for the destruction of neurons in the brain, which are of central importance for the function of the organ. Multiple sclerosis is a disease that usually affects young adults and accompanies them throughout their lives. The illness can severely restrict the professional and personal development of those affected. To date there is no curative treatment. Most of the treatments available are expensive and they can only slow down the progression of the disease. Therefore, it is of enormous socioeconomic importance to gain progress on the pathophysiological basis of the chronic disease.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The project developed experimental models that make it possible to largely reproduce human disease and tissue destruction. It has been shown that brain-specific T cells, which are important for the initiation of CNS autoimmune disease, can also cause progressive destruction of neurons. Methodological tools have also been developed to determine the molecular basis of this T cell-induced neuronal destruction.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

In the search for factors that control the pathogenic and destructive potential of brain-specific T cells in the CNS, an unexpected connection to the lungs was found. The newly discovered lung-brain axis is based on the composition of the lung microbiota. This determines how microglia – the brain’s resident immune cells – can react to inflammatory stimuli. By manipulating the lung microbiota, the susceptibility to developing autoimmune inflammation could be regulated. Ongoing studies should make it possible to reveal further new aspects of the cellular and molecular basis for the progressive neuronal destruction in CNS autoimmunity.

T cells (green) in contact with a neuron (red)