The immune system protects our body not only against pathogens, it also responds to various non-infectious environmental influences, such as food components, allergens and environmental toxins. In addition, metabolites generated in the organism itself, may significantly influence immune regulation. A dysfunction of immune homeostasis can lead to allergies or autoimmune diseases but also to immunodeficiencies with a higher risk of susceptibility to infection. Our work group is especially interested in the function and migration of dendritic cells, which act as important immune regulators in barrier organs, such as the skin or the mucosa. Moreover, we also investigate the function of monocytes and macrophages as modulators of the innate and adaptive immune response using conditional knockout models.
The chemokine CCL17 and CCL22 are mainly produced by myeloid cells and support the interaction with T cells in order to regulate adaptive immune responses. We could demonstrate that CCL17 reinforces the development of allergic reactions in the skin, as it supports, after allergen exposure, the emigration of Langerhans cells from the skin into the draining lymph nodes and subsequently the stimulation of allergen-specific T cells. Both chemokines also participate in the formation of an immune response to intestinal bacterial infections, such as Salmonella infection. Interestingly, we also discovered expression of CCL17 in the brain, particularly in pyramidal neurons of the hippocampus. Here, CCL17 appears to play an important role in the communication between neurons and microglia.
Myeloid cells of the skin and of the intestinal mucosa also express the aryl hydrocarbon receptor (AhR) and its repressor (AhRR). The AhR is a ligand-activated transcription factor, which recognizes small polyaromatic chemicals. Typical AhR ligands are known as environmental toxins, such as dioxin, but many other physiological ligands exist, representing natural food components or endogenous metabolic products. We investigate the immune regulatory function of the AhR/AhRR system in connection with allergies and infectious diseases. Furthermore, we analyze the influence of AhR/AhRR-dependent transcriptional regulation on the development of metabolic syndrome upon uptake of high-caloric diet. We hypothesize that cellular metabolism is regulated by the strength of AhR/AhRR signaling in a cell-type specific manner, indicating that environmental factors may exert a direct influence on development of obesity.