Human T cell regulation – from the mechanistic basis to translational applications
The major focus of our department is to investigate the regulation of human T cells in health and disease. We address fundamental questions about the mechanistic basis of human T cell memory formation, stabilization, and modulation. We also investigate T cell communication with the local tissue microenvironment in settings of health and disease. Our research has unraveled novel T cell specializations such as GM-CSF production (Noster et al. Sci Transl Med 2014) and anti-inflammatory Th17 cells (Zielinski et al. Nature 2012) with major implications for chronic infections and the pathogenesis of autoimmune diseases such as multiple sclerosis.
We are in particular interested in the mechanisms by which a tissue resident immunological memory is generated and maintained in the human tissue. The reciprocal interactions of T cells with the tissue micro-milieu including the microbiota as well as metabolites and even ions are of particular interest. They shape the functionality of the tissue resident memory T cell compartment, “imprint” tissue-tropic migration and residence and represent interesting targets for novel immunomodulatory therapies in settings of autoimmunity, cancer, and chronic infections.
To address our goals, we use a translational approach, combining the analysis of healthy and pathological tissue samples with novel cutting-edge technologies, gene editing and high-dimensional data analysis. We are studying patients undergoing extensive in vivo perturbation of their immune system, i.e. by systemic therapies with immunomodulatory drugs (biologics) or by stem cell transplantation. We also take advantage of studying patients with genetic immunodeficiency syndromes.
Together, our research aims to provide a fundamental basis of human T cell regulation and translational applications for the design of pharmaceutical targets and adoptive T cell therapies in settings of autoimmunity, infections, and cancer.