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Review
. 2021 Feb;18(2):259-268.
doi: 10.1038/s41423-020-00585-5. Epub 2021 Jan 6.

The aryl hydrocarbon receptor and the gut-brain axis

Andreia Barroso  1 , João Vitor Mahler #  1   2 , Pedro Henrique Fonseca-Castro #  1   2 , Francisco J Quintana  3   4
Affiliations
Review

The aryl hydrocarbon receptor and the gut-brain axis

Andreia Barroso et al. Cell Mol Immunol. 2021 Feb.

Abstract

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor initially identified as the receptor for dioxin. Almost half a century after its discovery, AHR is now recognized as a receptor for multiple physiological ligands, with important roles in health and disease. In this review, we discuss the role of AHR in the gut-brain axis and its potential value as a therapeutic target for immune-mediated diseases.

Keywords: Aryl hydrocarbon receptor; Autoimmune diseases; Infectious diseases; cancer.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
AHR and its signaling pathway. A Schematic representation of AHR protein domains. B The AHR signaling pathway. The inactive form of AHR is localized in the cytosol in a complex composed of HSP90, AIP, p23, and c-SRC. AHR agonists induce conformational changes in AHR that result in its translocation to the nucleus. In the nucleus, AHR interacts with ARNT, and the heterodimer is responsible for the transcription of XRE-containing genes. Notes: (AHR) aryl hydrocarbon receptor, (N) N terminal motif, (C) C terminal motif, (NLS) nuclear localization signal, (bHLH) basic-helix loop helix, (PAS) Per-Arnt-Sim, (Q-rich) glutamine rich, (HSP90) heat shock protein 90, (AIP) AHR-interacting protein, (XRE) xenobiotic responsive elements, (AHRR) AHR repressor, (CYP) cytochrome P450, (IDO) indoleamine 2,3-dioxygenase
Fig. 2
Fig. 2
Role of AHR in infections targeting the CNS. AHR can affect the outcome of infectious diseases that target the CNS. Notes: (NP) nanoparticles, (ROS) reactive oxygen species, (NO) nitric oxide
Fig. 3
Fig. 3
Role of AHR in glioblastoma. Kynurenine in the tumor microenvironment activates AHR in TAMs, promoting expression of CCR2, CD39 and KLF4. CCR2 contributes to the recruitment of TAMs to the tumor microenvironment, CD39 promotes CD8+ T-cell dysfunction, and KLF4 together with SOCS2 influences TAM polarization. Notes: (Kyn) kynurenine, (TAM) tumor-associated macrophages
Fig. 4
Fig. 4
AHR sensor and immunomodulatory roles. AHR senses diverse environmental cues provided by the diet, microbiome, and anthropogenic compounds. AHR signaling participates in physiological and pathological processes, making it a potential target for therapeutic intervention
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