Investigation of the local immune system regulation in COVID-19 Group Krebs The mechanisms leading to severe inflammatory lung disease in some COVID-19 patients are unknown. In this project, we will analyze the cells in the lung lavage of these patients and compare these findings with results from collaborators working on a mouse model of COVID-19. We hope so to reveal targets for COVID-19 therapy. Graphical abstract
Role of cytokine signaling for immunopathology and tumor development Group Krebs Inflammation is a driver of cancer. We have shown that IL-33 signaling is important for the development of myeloproliferative neoplasms (MPN), a type of blood cancer, and for promoting colorectal cancer (CRC) (Mager, J Clin Invest, 2015; Mertz, OncoImmunology, 2015; Pastille, Mucosal Immunol, 2019). We currently investigate the contribution of IL-33 to MPN progression and to the cellular and molecular mechanisms underlying IL-33-dependent CRC. For these studies, we use patient-derived samples and mouse models. Increased levels of IL-33 protein in bone marrow of MPN patients. IL-33: brown; CD34 (endothelial cells): red
mRNA splicing and epithelial integrity Group Krebs The intestinal barrier is often disrupted during intestinal diseases, causing gut leakiness. We have recently shown that the protein ESRP1, a regulator of mRNA splicing in epithelial cells, has a critical function to maintain the integrity of the intestinal barrier (Mager et al., eLife, 2017). In this project, we further investigate how loss or reduction of ESRP1 leads to intestinal homeostasis and pathogenesis, including inflammatory bowel disease and colorectal cancer. Bacteria (white arrows) penetrate the leaky intestinal barrier of Esrp1 mutant mice. Scale bars: 100 μm (from Mager et al., eLife, 2017)
Cross-talk between innate and adaptive immunity Group Krebs The vertebrate immune system comprises the innate immune system, providing the first line of defense, and the adaptive immune system, which is triggered at a later stage and that is responsible for memory. In this project, we use different murine models to better understand how innate immune cells modulate adaptive immune responses in dependence on the inflammatory environment, in infectious (e.g. after infection with a pathogen; Cardoso Alves, EMBO Reports, 2020) or sterile (e.g. for tumor surveillance) situations. TRAIL programs NK cells by blocking the production of inflammatory messengers (IFNγ) but promoting the formation of cell toxins (GZMB). NK cells lacking TRAIL produce more IFNγ but less GZMB, which results in greater antivirus CD8+ T cell response in infected mice
Seal of excellence award Robert Gaultney, PhD, received a Seal of excellence award for his Marie Skłodowska-Curie fellowship application (H2020-MSCA-IF-2020).
Lutz Zwillenberg Prize Lukas Mager In his PhD thesis entitled „Molecular Dissection of Inflammation-induced Immunopathologies“, Lukas Mager reveals an inflammatory mechanism that promotes blood as well as colon cancer. A molecular messenger, the so-called interleukin-33 (IL-33), plays an essential role in these diseases by activating immune cells and other cells in the tumor environment. This leads to the release of different growth factors triggering tumor growth. Therefore, IL-33 may represent a target for the therapy of these cancers.
