Aryl hydrocarbon receptor and intestinal immunity

Abstract

Aryl hydrocarbon receptor (AhR) is a member of the basic helix-loop-helix-(bHLH) superfamily of transcription factors, which are associated with cellular responses to environmental stimuli, such as xenobiotics and oxygen levels. Unlike other members of bHLH, AhR is the only bHLH transcription factor that is known to be ligand activated. Early AhR studies focused on understanding the role of AhR in mediating the toxicity and carcinogenesis properties of the prototypic ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In recent years, however, it has become apparent that, in addition to its toxicological involvement, AhR is highly receptive to a wide array of endogenous and exogenous ligands, and that its activation leads to a myriad of key host physiological functions. In this study, we review the current understanding of the functions of AhR in the mucosal immune system with a focus on its role in intestinal barrier function and intestinal immune cells, as well as in intestinal homeostasis.

Impaired Aryl Hydrocarbon Receptor Ligand Production by the Gut Microbiota Is a Key Factor in Metabolic Syndrome

“…A group of microbiota metabolites, such as those produced through metabolism of tryptophan from dietary sources, has been shown to signal through the aryl hydrocarbon receptor (AhR) (Zelante et al, 2013). AhR activation leads to several cellular responses and pathways including hormone and immune responses (Furue et al, 2014;Hao and Whitelaw, 2013;Leavy, 2011;Murray et al, 2014;Lamas et al, 2018), and thus can greatly influence health and disease risks. Indeed, we recently showed that the inefficiency of gut microbiota to produce tryptophan-based AhR ligands is involved in the pathogenesis of inflammatory bowel disease, notably through impairment of interleukin (IL)-22 production (Lamas et al, 2016).…”

Aryl hydrocarbon Receptor activation during in vitro and in vivo digestion of raw and cooked broccoli (brassica oleracea var. Italica)

“…Flavonoids are also reported as AhR ligands. 59 In the present study, it is apparent that the level of such flavonoids is too small to produce activation of AhR in our in vitro assay and in ileostomy samples. We have previously measured the activation induced by quercetin, a flavonoids relatively abundant in broccoli in our previous study and could not find a significant activation from it.…”

Development of an Indigo Naturalis Suppository for Topical Induction Therapy in Patients with Ulcerative Colitis

“…Regarding the mechanisms of IN, which mainly consists of several AhR ligands, such as indigo and indirubin, AhR ligands are known to promote mucosal healing via IL-22 from group 3 innate lymphoid cells [10,11,28,29]. Therefore, the efficacy of IN is mainly assumed to be associated with the AhR pathway.…”