Aryl Hydrocarbon Receptor Signaling in Immune Responses

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that integrates environmental, dietary and microbiota-derived signals to shape both innate and adaptive immune responses. Upon binding endogenous or exogenous ligands, AHR translocates to the nucleus, dimerises with ARNT and modulates genes involved in xenobiotic metabolism, cytokine production and cell differentiation. In barrier tissues such as the skin and gut, AHR regulates epithelial integrity and inter-compartmental communication between epithelial cells and resident immune populations. In lymphoid organs, AHR influences T cell fate decisions, notably the balance between regulatory T cells and Th17 cells, and cross-talks with other transcriptional programmes including NF-κB. Dysregulation of AHR signalling is implicated in chronic inflammatory and autoimmune diseases, infection susceptibility and tumourigenesis. Conversely, targeted modulation of AHR by selective agonists or antagonists offers therapeutic opportunities across inflammatory skin disorders, gastrointestinal inflammation and systemic immune dysregulation. Emerging evidence also highlights inter-individual variation in AHR pathway components and ligand availability as determinants of immune resilience or pathology, underscoring the global significance of AHR as a nodal point in environmental immunology.

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Aryl Hydrocarbon Receptor Signaling in Immune Responses publication trend

The graph below shows the total number of articles in aryl hydrocarbon receptor signaling in immune responses across all publications each year (not limited to Nature Index journals).

Technical terms

Aryl hydrocarbon receptor (AHR): A ligand-activated transcription factor that senses environmental and endogenous compounds to regulate gene expression.

Ligand: A molecule that specifically binds to a receptor to initiate downstream signalling.

Cytochrome P450 enzymes: A family of monooxygenases that metabolise xenobiotics and regulate the availability of AHR ligands.

Regulatory T cells (Tregs): A subset of T lymphocytes that suppress excessive immune responses to maintain self‐tolerance and prevent autoimmunity.

Type 17 T helper cells (Th17): A subset of T lymphocytes producing interleukin-17, involved in host defence and inflammatory pathology.

Nuclear factor kappa B (NF-κB): A transcription factor controlling expression of pro-inflammatory genes and interacting with AHR signalling.

References

1. Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles. Scientific Reports (2015).
2. Cross-talk between Aryl Hydrocarbon Receptor and the Inflammatory Response A ROLE FOR NUCLEAR FACTOR-κB* * This work was supported, in whole or in part, by NIEHS, National Institutes of Health Grants R01 ES019898-02 (to C. F. A. V.) and R01 ES007685 (to M. S. D.).. Journal of Biological Chemistry (2013).
3. The Role of the Aryl Hydrocarbon Receptor (AHR) in Immune and Inflammatory Diseases. International Journal of Molecular Sciences (2018).
4. Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis. International Journal of Molecular Sciences (2019).
5. The Environmental Sensor AHR Protects from Inflammatory Damage by Maintaining Intestinal Stem Cell Homeostasis and Barrier Integrity. Immunity (2018).
6. Benzo[a]pyrene—Environmental Occurrence, Human Exposure, and Mechanisms of Toxicity. International Journal of Molecular Sciences (2022).