Investigations

In autoantibody-mediated gliopathies, such as Neuromyelitis Optica Spectrum Disorder, pathology often spreads quickly beyond the intital target cell type to affect other glial cells. In this project, we will identify glial-glia interactions that act either as checkpoints of acute pathology spread or as checkpoints of lesion repair. To achieve this, we will use in vivo imaging in animal models, as well as genetic interventions and close correlation with human neuropathology, to study how the ...

B lymphocytes have been more recently recognized to possess a dual role in MS pathogenesis. On the one hand, B cells promote inflammation of the central nervous system and MS progression, while on the other hand, B-lymphoid inhibition of pathogenic T cell functions ameliorates MS severity and facilitates recovery from acute MS bouts. To understand the functional dichotomy, we aim at a comprehensive phenotyping of individual B cell subpopulations followed by their transcriptional profiling to ...

The cerebral cortex contains a special, perineuronally localized population of oligodendrocyte lineage cells with possible functions in connectivity and myelination. We hypothesize that this cell population serves as a reservoir of remyelinating cells after myelin damage. We will apply spatial transcriptome analysis with subcellular resolution in experimental models of demyelination and human tissue from patients with multiple sclerosis to define physiological and pathological states of perineuronal ...

Demyelinating injuries in the central nervous system trigger a regenerative process that relies on coordinated responses from multiple cell types, including the innate immune system. Here, we propose that a maladaptive chronic immune response may be initiated when microglia’s capacity to clear myelin debris is overwhelmed, leading to a self-propagating immune response that impairs remyelination and causes further tissue damage. We aim to identify the molecular checkpoints in microglia/macrophages ...

Compartmentalized inflammatory processes within the CNS might be a driver of tissue damage in chronic stages of CNS autoimmunity. Tissue resident T cells constitute a sizeable population of immune cells in the chronically inflamed CNS. However, little is known about their functional integration into CNS tissue niches. Here, we have identified the co-inhibitory molecule CD96 to be expressed on a subset of CNS resident conventional and regulatory T cells. Using genetic tools, we aim to investigate ...