Journal Article (Review Article)

DKFZ-2026-00142

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The aryl hydrocarbon receptor: structure, signaling, physiology and pathology.

Coumoul, X. ; Barouki, R. ; Esser, C. ; Haarmann-Stemmann, T. ; Lawrence, B. P. ; Lehmann, J. ; Moura-Alves, P. ; Murray, I. A. ; Opitz, C.DKFZ* ; Perdew, G. H. ; Bourguet, W.

2026
Macmillan Publishers, part of Springer Nature London

Abstract: The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor of the bHLH/PAS protein family. In this review, we explore the multifaceted roles of AHR in both health and disease, tracing its recognition as a xenobiotic sensor and a central regulator of physiological homeostasis. We begin by recounting six decades of discoveries that have shaped our understanding of AHR, from its canonical function in environmental sensing to its critical roles in development, immune regulation, barrier tissue integrity, and host-microbe interactions. We detail recent structural breakthroughs that have illuminated the ligand-binding mechanisms and regulation of AHR, providing key insights into its activation and transcriptional control. We also highlight the diversity of AHR ligands, ranging from environmental toxins to microbial and dietary metabolites of tryptophan, and their context-dependent effects on AHR activation through the canonical pathway and noncanonical signaling mechanisms. We examine the involvement of AHR in pathologies such as cancer and autoimmune and inflammatory diseases and its potential as a therapeutic target. Finally, emphasis is placed on recent advances and future developments in drug design, aiming to develop modulators with clinical efficacy. This comprehensive synthesis underscores the dual role of AHR as a master integrator of both environmental and endogenous cues. Placing AHR within broader frameworks, such as the exposome, opens new avenues for therapeutic innovation and more effective strategies for disease prevention.

Keyword(s): Receptors, Aryl Hydrocarbon: genetics (MeSH) ; Receptors, Aryl Hydrocarbon: chemistry (MeSH) ; Receptors, Aryl Hydrocarbon: metabolism (MeSH) ; Humans (MeSH) ; Signal Transduction: genetics (MeSH) ; Neoplasms: genetics (MeSH) ; Neoplasms: pathology (MeSH) ; Neoplasms: metabolism (MeSH) ; Animals (MeSH) ; Inflammation: genetics (MeSH) ; Inflammation: pathology (MeSH) ; Inflammation: metabolism (MeSH) ; Autoimmune Diseases: genetics (MeSH) ; Autoimmune Diseases: pathology (MeSH) ; Autoimmune Diseases: metabolism (MeSH) ; Basic Helix-Loop-Helix Proteins: genetics (MeSH) ; Ligands (MeSH) ; Receptors, Aryl Hydrocarbon ; AHR protein, human ; Basic Helix-Loop-Helix Proteins ; Ligands

Note: #DKTKZFB26#

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Contributing Institute(s):

1. Metabolischer Crosstalk bei Krebserkrankungen (B350)
2. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2026

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Database coverage:
; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 30 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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