Project R-10925

Inflammasome activation in TH lymphocytes, induced by mitochondrial impairment, causes local tissue damage in the brain of multiple sclerosis patients. (Research)

Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), characterized by infiltration of immune cells in the brain. The disease is initiated when self-reactive T lymphocytes are activated after recognizing brain proteins, after which they travel to the brain through the blood brain barrier (BBB). Once inside the CNS, these cells attack neuronal tissue resulting in neurological disabilities such as visual problems and paralysis. After years of the initial phase of the disease (relapsing-remitting MS), most patients progress into a secondary-progressive phase, leading to accumulating disability. At the moment, there is a lack of treatment options for progressive MS patients. We and others have previously found that cytotoxic CD T lymphocytes, as well as mitochondrial impairment, correlate to progression of disease. Interestingly, mitochondrial impairment was also shown to induce inflammasome activation in T lymphocytes. In this project, I identify whether inflammasome activation in TH lymphocytes, induced by mitochondrial impairment, is increased in MS patients, and whether it contributes to disease pathogenesis and progression by causing local tissue damage in the brain.

01 November 2020 - 31 October 2024