The influence of AHR on immune and tissue biology

Abstract

The aryl hydrocarbon receptor is a ligand dependent transcription factor which functions as an environmental sensor. Originally discovered as the sensor for man made pollutants such as 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) it has recently gained prominence as an important mediator for environmental triggers via the diet or microbiota which influences many physiological functions in different cell types and tissues across the body. Notably AHR activity contributes to prevent excessive inflammation following tissue damage in barrier organs such as skin, lung or gut which has received wide attention in the past decade. In this review we will focus on emerging common AHR functions across cell types and tissues and discuss ongoing issues that confound the understanding of AHR physiology. Furthermore, we will discuss the need for deeper molecular understanding of the functional activity of AHR in different contexts with respect to development of potential therapeutic applications.

Keywords: Aryl Hydrocarbon Receptor; Barrier Organs; Cytochrome P4501; Intestinal Epithelium; Tissue Repair.

Figure 1. Expression of AHR across murine tissues.

Sections from different organs collected from a 12-week-old AHR reporter mouse (Diny et al, 2022) (AHR-td-Tomato) stained with different antibodies and DAPI as indicated in each panel.

Figure 2. Distribution of AHR2 activation in zebrafish embryos after exposure to FICZ and TCDD.

Images of a Cyp1a reporter strain (Tg(Cyp1a:EGFP)) exposed to FICZ (50 nM) and TCDD (0.01 nM), respectively, from 1 day post fertilisation through the embryo water. At 2 and 4 days of exposure, images were taken by confocal microscopy. In the case of FICZ, AHR2 activation was restricted to the outer barrier on day 2, of which very little was remaining on day 4. In contrast, TCDD caused an activation mainly in internal organs already at day 2, especially in the liver and gills, which was still strong at day 4, when also the intestinal tract was highly activated.