Der Wirtsstoffwechsel als antimikrobieller Effektor (Metabodefense)
01/2020 - 12/2024
Starting September 2022, researchers from the Charité – University Medicine Berlin, University of Regensburg, University Clinic Erlangen, Helmholtz Center for Infectious Research, Max-Delbrück-Center for Molecular Medicine, and the German Aerospace Center will investigate the role of the aryl hydrocarbon receptor (AhR) in inflammation as a function of nutrition. The interdisciplinary collaborative project TAhRget (Targeting AhR-dependent Inflammation for Organ Protection) will be managed by the Experimental and Clinical Research Center (ECRC) – a joint clinical research center of the Charité and the Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association. The Federal Ministry of Education and Research (BMBF) will fund the project with approximately three million euros.
Many chronic and autoimmune diseases are accompanied by persisting or episodic inflammation that can lead to severe organ damage. The AhR, which is found in a multitude of body- and immune cells and plays an important role in the elimination of exogenous substances, is associated with such inflammatory processes. However, the underlying mechanisms are not yet fully understood. TAhRget aims at elucidating the joint role of the AhR and nutrition in the development of inflammation in chronic kidney disease (CKD) and multiple sclerosis (MS). Against the background of these very distinct diseases, researchers hope to gain better insight into the spectrum of ligands and activities of the AhR with the ultimate goal of elucidating the potential of the AhR as a target for controlling or even inhibiting inflammatory processes and thereby caused organ damage.
With the use of patient cohorts, animal models, cultured cells, and single cell analyses as well as microbiome and nutrition studies the research team aims to find out, whether and to which extent the AhR contributes to organ damaging inflammatory processes in CKD and MS. Another goal is the identification of biomarkers indicative of AhR activity. It is known, that the AhR is capable of binding exogenous compounds such as food components and metabolic products of gut bacteria to facilitate their excretion. Further, nutritional studies have already shown, that dietary changes can exert beneficial effects on chronic inflammatory diseases that are likely to be mediated by the AhR. Therefore, a major focus of the planned investigation will be diet and microbiota mediated processes that modulate the AhR and concomitant inflammatory processes. Thereby, TAhRget hopes to discover which food components, metabolic products and diets have detrimental and beneficial effects on AhR-mediated inflammatory processes, respectively, in order to exploit them in the future in the personalized treatment of patients suffering from chronic inflammatory diseases. To accomplish this goal, nephrologists and neurologists will join forces with immunologists, microbiologists, biochemists and nutritionists to gain groundbreaking knowledge on the contribution of the AhR to chronic inflammation and novel strategies to fight inflammation.
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