The immune system is required to survey the central nervous system (CNS) and protect it from infectious diseases. However, immune surveillance of the CNS is delicate because the brain and the spinal cord do not tolerate immune mediated tissue damage. Uncontrolled adaptive immune responses in the CNS cause serious disease conditions including multiple sclerosis and neuromyelitis optica. It is our aim to characterize the properties of T cells that induce tissue damage in the CNS and to understand how they are regulated. To this end, we pursue four major areas of research as outlined below.
Th1 cells and Th2 cells communicate with other immune cells and are required for host defense against intracellular pathogens and parasites, respectively. In contrast, Th17 cells are different because they communicate with tissue cells and induce severe immunopathology in autoimmune diseases including multiple sclerosis. We have a long standing interest in the differentiation and biology of Th17 cells. IL-6 is a non-redundant factor for the differentiation of Th17 cells, and we have developed tools to investigate the cellular sources of IL-6 and its signaling modalities in the context of the generation of Th17 cells in vivo in animal models for multiple sclerosis.
Regulatory T cells
Adaptive immune responses in the CNS are highly regulated. This regulation takes place by the "re-programming" of pathogenic effector T cells into IL-10 producing T cells but also by "professional" regulatory T cells like Foxp3+ Tregs. In specific anatomical niches (e. g. in the colon) Foxp3+ Tregs can be generated outside the thymus. However, Foxp3+ Tregs that are found in the inflamed CNS are thymus derived (so-called naturally occurring Tregs). We are interested in how these Tregs acquire their regulatory function in the inflamed CNS. We are aiming at understanding whether Tregs in the CNS have functions in tissue homeostasis beyond the regulation of inflammation.
Immune cell trafficking
The provenance of immune cells recruited to the CNS during autoimmune inflammation is not clear. For example, while the gut microbiome has been shown to influence immune responses in distant organs, it is not understood by which mechanisms "environmental cues" imprint certain properties in immune cells and whether these immune cells then physically migrate to distant organs to contribute to tissue homeostasis or induce immune pathology. Here, we are developing genetic tools to mark immune cells site-specifically in order to trace them over short and long periods of time and in various anatomical compartments.
Tissue immune monitoring promises to be an excellent means to stratify patients with neuroimmunologic disorders for immune intervention strategies with the most favorable risk/benefit ratio. Using novel imaging technologies including optical coherence tomography (OCT), we aim to better understand the in situ immunologic correlate of distinct imaging signals. We investigate these questions in models of multiple slcerosis and neuromyelitis optica.