Use of natural AhR ligands as potential therapeutic modalities against inflammatory disorders

Abstract

The aim of this review is to discuss research involving ligands for the aryl hydrocarbon receptor (AhR) and their role in immunomodulation. While activation of the AhR is well known for its ability to regulate the biochemical and toxic effects of environmental chemicals, more recently an exciting discovery has been made indicating that AhR ligation can also regulate T-cell differentiation, specifically through activation of Foxp3+ regulatory T cells (Tregs) and downregulation of the proinflammatory Th17 cells. Such findings have opened new avenues of research on the possibility of targeting the AhR to treat inflammatory and autoimmune diseases. Specifically, this review will discuss the current research involving natural and dietary AhR ligands. In addition, evidence indicating the potential use of these ligands in regulating inflammation in various diseases will be highlighted. The importance of the AhR in immunological processes can be illustrated by expression of this receptor on a majority of immune cell types. In addition, AhR signaling pathways have been reported to influence a number of genes responsible for mediating inflammation and other immune responses. As interest in the AhR and its ligands increases, it seems prudent to consolidate current research on the contributions of these ligands to immune regulation during the course of inflammatory diseases.

Secondary Plant Metabolites for Sun Protective Cosmetics: From Pre-Selection to Product Formulation

“…AhR can also cross-talk and directly interact with proteins involved in major redox-regulated signalling pathways such as NF-kappaB and various kinases, such as Src, JNK, p38, MAPK and with oestrogen receptors to mediate oestrogen metabolism [61]. Recent studies have unraveled unsuspected physiological roles and novel alternative ligand-specific pathways for this receptor that allowed for hypothesising numerous pharmacological roles of AhR ligands useful for the development of a new generation of photo-protective drugs and cosmetics [62,63].…”

Proteomic pathway analysis of the hippocampus in schizophrenia and bipolar affective disorder implicates 14-3-3 signaling, aryl hydrocarbon receptor signaling, and glucose metabolism: Potential roles in GABAergic interneuron pathology

“…Based on these results, interference with AHR-mediated signaling could yield therapeutic effects in psychiatric disorders (Busbee et al, 2013;Linden et al, 2010;Quintana, 2013).…”

3,3′-Diindolylmethane Ameliorates Experimental Autoimmune Encephalomyelitis by Promoting Cell Cycle Arrest and Apoptosis in Activated T Cells through MicroRNA Signaling Pathways

“…More recently, the use of plant-derived indoles, such as 3,39-diindolylmethane (DIM), which are found in cruciferous vegetables, and other similarly structured compounds, have been reported as a potential therapeutic modality against inflammatory disorders (Busbee et al, 2013). Data from various cancer studies, which include prostate (Nachshon-Kedmi et al, 2003), colon (Lerner et al, 2012), and gastric (Li et al, 2013) cancers, have collectively suggested that DIM also acts on a number of molecular pathways centered on cellular proliferation and survival to mediate its effects.…”