Aryl hydrocarbon receptor restrains tonic cytokine responses by inhibiting microbiota sensing in monocytes
Immune cells are constantly exposed to microbiota-derived compounds that can engage innate recognition receptors. How this constitutive stimulation is downmodulated to avoid systemic inflammation and autoimmunity is poorly understood. Here, we show that aryl hydrocarbon receptor (AhR) deficiency in monocytes unleashed spontaneous cytokine responses in vivo, driven by stimulator of interferon genes (STING)-mediated tonic sensing of microbiota. This effect was specific to monocytes, as mice deficient for AhR specifically in macrophages did not show any dysregulation of tonic cytokine responses. AhR inhibition also increased tonic cytokine production in human monocytes. Finally, in patients with systemic juvenile idiopathic arthritis, low AhR activity in monocytes correlated with elevated cytokine responses. Our findings reveal an essential role for AhR in monocytes in restraining tonic microbiota sensing and in maintaining immune homeostasis.
Authors
- Alice Coillard (ORCID: https://orcid.org/0000-0001-6309-5754)
- Alma‐Martina Cepika (ORCID: https://orcid.org/0000-0003-2862-1901)
- Marianne Burbage (ORCID: https://orcid.org/0000-0003-0686-2608)
- Romain Banchereau (ORCID: https://orcid.org/0000-0001-6916-6445)
- Burkhard Becher (ORCID: https://orcid.org/0000-0002-1541-7867)
- Élodie Segura (ORCID: https://orcid.org/0000-0003-1795-1921)
- Alba de Juan (ORCID: https://orcid.org/0000-0003-0174-4389)
- Alessandra Rigamonti (ORCID: https://orcid.org/0000-0002-1938-2278)
- Christel Goudot (ORCID: https://orcid.org/0000-0001-6037-2314)
- Adeline Cros (ORCID: https://orcid.org/0000-0002-2100-7290)
- Virginia Pascual (ORCID: https://orcid.org/0000-0002-2274-7979)
- Darawan Tabtim-On (ORCID: https://orcid.org/0000-0003-4914-2088)
- Mathilde Rieux-Laucat
- Emeline Papillon
Institutions
- Inserm (FR)
- University of Zurich (CH)
- Université Paris Cité (FR)
- Université Paris Sciences et Lettres (FR)
- Institut Necker Enfants Malades (FR)
- Baylor Institute for Rehabilitation (US)
- Institut Curie (FR)
Publication Details
- Journal
- Journal of Clinical Investigation
- Published
- 2025-10-02
- DOI
- https://doi.org/10.1172/jci189937
- Citations
- 1
- Primary Topic
- Tryptophan and brain disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.58
Funders
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale
- Institut National Du Cancer
- National Institutes of Health
- HORIZON EUROPE Marie Sklodowska-Curie Actions