How a receptor contributes to inflammation
Joint press release with Charité – Universitätsmedizin Berlin
Many chronic illnesses and autoimmune diseases are accompanied by sustained or recurrent episodes of inflammation that can lead to severe organ damage. Chronic inflammation of this kind is linked to the aryl hydrocarbon receptor (AhR), which is found in a variety of cells in our body and immune system and helps to eliminate foreign substances. However, the mechanisms at work have not yet been sufficiently studied.
We want to find out if AhR is suitable as a therapeutic target for treatments.
Now TAhRget (Targeting AhR-dependent Inflammation for Organ Protection), a consortium project under the aegis of Charité – Universitätsmedizin Berlin, is investigating the role of AhR and diet in the development of inflammation, focusing on the examples of chronic kidney disease (CKD) and multiple sclerosis (MS). The German Federal Ministry of Education and Research (BMBF) is providing about three million euros in funding. The project is led by the Experimental and Clinical Research Center (ECRC) – a joint institution of Charité and the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC).
Studying two such different diseases, the researchers hope to get a clearer picture of AhR’s binding and efficacy spectrum. “We want to find out if AhR is suitable as a therapeutic target for treatments that keep inflammatory processes in check and minimize if not eliminate organ damage,” says Dr. Nicola Wilck, head of a lab at the ECRC, a specialist at Charité’s Department of Nephrology and Medical Intensive Care, and the project’s coordinator.
Considering diet in treatment
Six partners from across Germany are represented on the interdisciplinary research team. In the next three years, it plans to use patient cohorts, animal models, cell cultures, single-cell analysis, and microbiome and dietary studies to find out if and to what extent AhR contributes to organ-damaging inflammation in chronic kidney disease and multiple sclerosis. The scientists will also search for reliable biomarkers that indicate AhR is at work. It is known that the receptor binds foreign substances – such as components of food and metabolic products of gut bacteria – to facilitate their elimination. Studies also show that dietary changes can have a positive influence on diseases that involve chronic inflammation.
“We suspect that AhR-mediated processes play a role. One focus of our research will therefore be on diet- and microbiome-related processes that regulate AhR and thus the inflammatory processes that occur in CKD and MS,” says Dr. Anja Mähler, head of the Clinical Research Unit at the ECRC and head of the TAhRget subproject dedicated to diet. The goal is to find out what food components, metabolic products, and dietary forms have a negative or a positive impact on AhR-mediated inflammatory processes, so that this knowledge can be applied to patient treatment in the future. Other TAhRget participants include the ECRC labs of Professor Dominik Müller and Professor Friedemann Paul, as well as ECRC scientists Dr. Victoria Parland, Dr. Chotima Böttcher, and Dr. Hendrik Bartolomaeus, who are each conducting independent subprojects.
“Our interdisciplinary team brings together clinicians from nephrology and neurology, immunologists, microbiome and metabolomic researchers, and dieticians,” Wilck says. “We hope that this collaborative and interdisciplinary research approach will let us gain new essential, pioneering insights into AhR’s contribution to chronic inflammation and thus pave the way for new treatment options.”
The consortium project TAhRget
The TAhRget project is funded under the BMBF call “Promotion of interdisciplinary consortia for research into pathomechanisms.” Charité - Universitätsmedizin Berlin is coordinating the interdisciplinary project, which brings together six partners. The project is led by the Experimental and Clinical Research Center (ECRC) – a joint institution of Charité and the MDC. Other partners include the Helmholtz Centre for Infection Research (HZI), Universitätsklinikum Erlangen, the German Aerospace Center (DLR), and the University of Regensburg. The project officially started on September 1, 2022.
Text: Nicole Silbermann, Charité
Further information
Charité’s Department of Nephrology and Medical Intensive Care
Contact
Dr. Nicola Wilck
Head of the ECRC lab “Immune-microbial dynamics in cardiorenal disease”
Charité – Universitätsmedizin Berlin | Experimental and Clinical Research Center (ECRC)
+ 49 30 450 540 459
nicola.wilck@mdc-berlin.de
