Periodic Reporting for period 2 - T-Neuron (T-cell-induced immune programming and degeneration of the neuronal tissue during chronic autoimmunity)
Reporting period: 2023-03-01 to 2024-08-31
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.
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.
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.