Systems Immunology

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Group Leader

Administration

Franziska Höltge
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Mission statement

Chronic inflammation is a sustained immunological reaction of the organism, which leads to tissue destruction and remodeling via uncontrolled long-term activation of immune effector mechanisms. These mechanisms represent the underlying pathophysiology of a group of socio-economically relevant disorders, which have been termed chronic inflammatory diseases (CID). CID have a lifetime prevalence of over 10% in the EU and a globally rising incidence in countries adopting the Western industrialized lifestyle.  

Our group focuses on inflammatory bowel disease (IBD with its two subentities Crohn´s disease and Ulcerative colitis) as an archetypal example of CID, where the exact cause of the sustained inflammation is unknown. An impaired interaction of the immune system with the resident microbiome at the gut epithelial barrier has emerged as an explanatory model of how the environment shapes detrimental immune responses. Consistent with this idea, IBD has been associated with an altered composition and function of the residing bacteria and, vice versa, microbiota are known to shape long-term gene expression programs of specific cell populations. At least in preclinical models, therapeutic targeting of the microbiota has been shown to exert beneficial influences on the underlying immune responses.  

  • Our mission is to understand precisely how the mucosal immune system and the environment are interacting to drive chronic inflammation. A clear focus is on epithelial cell function, which we regard as a pivotal intermediate layer transmitting and licensing luminal information to the underlying migratory immune cells.  

  • We aim to identify actionable disease markers and pathways states to predict progression and provide rationale for individual therapeutic targets. This requires the integration of molecular information across multiple scales from singular pathways to cells and to the human organism as a whole.  

  • We thus use systems-oriented approaches and a wide range of technologies including single cell-based transcriptomics and epigenomics as well as bacterial functional genomic profiling. Our projects aim to provide detailed mechanistic insights into skewed immune responses that ultimately will be translated into the clinic to improve therapy of CID patients. 

  • We employ large-scale human cohort studies, but also develop innovative preclinical model systems such as iPSC and organoid-based cellular models to assess individualized therapeutic targets (“clinical studies in a dish”). 

                                  

 

Our Junior Research Groups:

Functional Host-Microbiome Research lead by Felix Sommer

Immunometabolism of intestinal inflammation lead by Konrad Aden