Functional changes in local T cells during onset vs. remission vs. relapse of colitis Group Müller Understanding the mechanisms that drive remission and relapsing of intestinal inflammation is a prerequisite for treating patients with inflammatory bowel diseases. We have recently established a reversible, relapsing-remitting mouse model of colitis with reproducible onset of intestinal inflammation, induction of remission and repeated flares of inflammation (Brasseit et al., Mucosal Immunol 2016). In this model we monitor the functional changes induced in the CD4 T cells during induction of colitis, during remission, and relapse of colonic inflammation at the single cell level, and in distinct CD4 T cell clones with identical T cell receptor. An ultimate goal is to identify strategies to specifically extend the remission period, or even prevent a further relapse of disease. In the healthy intestine, luminal bacteria are separated by a mucus layer (green) from the epithelium (blue), containing mucus-secreting goblet cells (green) and the lamina propria, containing numerous immune cells
TREM-1 as an amplifier of inflammation in immunosurveillance and immunopathologies Group Müller TREM-1 (Triggering Receptor Expressed on Myeloid Cells-1) is an activating innate immune receptor on neutrophils and monocytes / macrophages. We previously described a critical pathogenic role for TREM-1 not only in acute, but also in chronic inflammation, notably, in inflammatory bowel diseases (Schenk et al., J Immunol 2005, J Clin Invest 2007). We generated a Trem1-/- mouse (Weber et al. 2014) to determine the Trem1-mediated effects in atherosclerosis (Zysset et al., Nat Comms 2016) and the development of colitis-associated colorectal carcinoma (Saurer and Zysset et al., Sci Rep 2017). Current research interests include collaborative efforts on the involvement of TREM-1 in neurological disorders, such as stroke (Liu et al., Nat Immunol 2019), and neurodegenerative disorders. TREM-1-activation on monocytes leads to an enhanced lipid uptake (red droplets) when cultured in the presence of dyslipidemic serum from ApoE-/- mice, maintained on a high fat/high cholesterol diet
Functional plasticity and retention of tissue-resident T-cells in the intestinal mucosa Group Müller Understanding the functions and the regulation of intestinal T cell subsets is one of our long-standing research objectives. Some of these T cells in the intestine represent the prototypical example of tissue-resident T cells due to their resident location at a barrier site, and their limited capacity to recirculate. Currently, we investigate the regulation of intestinal resident T cells in the protective immunity against pathogens (e.g. infection with Listeria monocytogenes), but also their contribution to the development of chronic inflammatory disorders. In particular, we investigate the molecular mechanisms that regulate their tissue-resident phenotype, and assess how distinct functional activities of this T cell subset may either result in protective immunity, or inflammatory pathologies. Intestinal tissue resident T cells show a unique molecular signature which is distinct from the core transcriptome in their circulating counterparts
Dr. Lutz Zwillenberg-Preis 2017 At the 183rd Dies Academicus of the University of Bern the Dr. Lutz Zwillenberg Prize for an outstanding publication or PhD thesis in Biological Sciences was awarded to Daniel Zysset, PhD, for his work “TREM-1 links dyslipidemia to inflammation and lipid deposition in atherosclerosis”.
