Role of AhR in Immuntoxicology
Team leader:
Team:
- Dr. Imke Bargen
- Katharina Haas, PhD student
- Rebecca Scholz, PhD student
- Katja Simon, PhD student
- Eva Padberg, MD student
- Babette Martiensen, VTMA
- Swantje Steinwachs, BTA
Our group is interested in the role of the aryl hydrocarbon receptor (AhR) for immune functions, in particular in the barrier organs skin and gut. AhR is a sensor of small chemical molecules and triggers adaptive responses by the cell, e.g. induction of enzymes, which degrade such chemicals. Moreover, the AhR seems have evolved to allow useful responses of cells to dietary components in the gut, and to chemicals generated by light in the skin. An import focus is the influence of AhR-signalling for the differentiation of cells, and for the function of dendritic cells in the context of allergy and tolerance.
Skin: role of AhR for differentiation and function of Langerhans cells
The skin is part of the immune system. Langerhans cells are professional antigen presenting cells which reside in the epidermis and act as sentinels for pathogens. Once activated they alarm T cells and thus trigger an appropriate immune response. We found that Langerhans cells express AhR at high levels, indeed need AhR expression for proper maturation and function. It is an important feature of dendritic cells in barrier organs that they can balance between necessary inflammatory immune responses and the need to dampen the immune system when danger is not at hand or over. Currently we follow up on the AhR-dependent expression of IDO, an enzyme involved in the immunosuppressive capacities of Langerhans cells. Understanding this pathway will be important in molecular preventive strategies aimed at manipulating unwanted allergic skin reactions.
Skin: Role of AhR for epidermal γδ- T-cells
The second type of immune cells in the epidermis are a special subset of T cells which all bear one type of T cell receptor made of g and d chains (rather than the a and b chains in most T cells). The antigen specificity of these cells is unknown, presumably they are stress proteins released by injured or stressed keratinocytes. gd T cells participate in "immunosurveillance" of the skin, and are thus important in protection against tumors, UV-damage, and in would healing. We recently reported that gd T cells are absent in the skin of AhR-deficient mice, caused by a failure to proliferate after homing to the skin. We investigate this further, with a focus on the functional consequences for skin health.
Gut: Role of AhR in oral tolerance
It has been known for long that toxic AhR-ligands such as the environmental pollutant "Dioxin" (a class of chemicals, whose most toxic member is 2,3,7,8-tetrachlorodibenzo-p-dioxin) are strongly immunosuppressive. We have recently reported that dioxin treatment leads to a break-down of oral tolerance. Oral tolerance is a vital feature of the immune system, making sure that there is no immune response against dietary proteins. While environmental dioxin exposure has decreased over the last years due to strong emission control, other AhR ligands are part of normal diets. Indeed, food supplements containing high amounts of natural AhR ligands are marketed. Recent studies have shown that such AhR-ligands are needed for the formation of the gut immune system. We are currently investigating the effects of AhR-ligands on oral tolerance further, i.e. look at the mechanisms and cell types responsible, the effects of natural ligands on oral tolerance, and will also investigate the consequences for food allergies.
