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ResearchIn-Press PreviewImmunologyInflammation Open Access | 10.1172/JCI189937

Aryl hydrocarbon receptor restrains tonic cytokine responses by inhibiting microbiota sensing in monocytes

Adeline Cros,1 Alessandra Rigamonti,1 Alba de Juan,1 Alice Coillard,1 Mathilde Rieux-Laucat,1 Darawan Tabtim-On,1 Emeline Papillon,1 Christel Goudot,1 Alma-Martina Cepika,2 Romain Banchereau,2 Virginia Pascual,2 Marianne Burbage,1 Burkhard Becher,3 and Elodie Segura1

1Institut Curie, PSL Research University, INSERM, U932, Paris, France

2Baylor Institute for Immunology Research, Dallas, United States of America

3Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland

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1Institut Curie, PSL Research University, INSERM, U932, Paris, France

2Baylor Institute for Immunology Research, Dallas, United States of America

3Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland

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1Institut Curie, PSL Research University, INSERM, U932, Paris, France

2Baylor Institute for Immunology Research, Dallas, United States of America

3Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland

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1Institut Curie, PSL Research University, INSERM, U932, Paris, France

2Baylor Institute for Immunology Research, Dallas, United States of America

3Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland

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1Institut Curie, PSL Research University, INSERM, U932, Paris, France

2Baylor Institute for Immunology Research, Dallas, United States of America

3Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland

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1Institut Curie, PSL Research University, INSERM, U932, Paris, France

2Baylor Institute for Immunology Research, Dallas, United States of America

3Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland

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1Institut Curie, PSL Research University, INSERM, U932, Paris, France

2Baylor Institute for Immunology Research, Dallas, United States of America

3Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland

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1Institut Curie, PSL Research University, INSERM, U932, Paris, France

2Baylor Institute for Immunology Research, Dallas, United States of America

3Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland

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1Institut Curie, PSL Research University, INSERM, U932, Paris, France

2Baylor Institute for Immunology Research, Dallas, United States of America

3Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland

Find articles by Cepika, A. in: PubMed | Google Scholar

1Institut Curie, PSL Research University, INSERM, U932, Paris, France

2Baylor Institute for Immunology Research, Dallas, United States of America

3Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland

Find articles by Banchereau, R. in: PubMed | Google Scholar

1Institut Curie, PSL Research University, INSERM, U932, Paris, France

2Baylor Institute for Immunology Research, Dallas, United States of America

3Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland

Find articles by Pascual, V. in: PubMed | Google Scholar

1Institut Curie, PSL Research University, INSERM, U932, Paris, France

2Baylor Institute for Immunology Research, Dallas, United States of America

3Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland

Find articles by Burbage, M. in: PubMed | Google Scholar

1Institut Curie, PSL Research University, INSERM, U932, Paris, France

2Baylor Institute for Immunology Research, Dallas, United States of America

3Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland

Find articles by Becher, B. in: PubMed | Google Scholar |

1Institut Curie, PSL Research University, INSERM, U932, Paris, France

2Baylor Institute for Immunology Research, Dallas, United States of America

3Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland

Find articles by Segura, E. in: PubMed | Google Scholar

Published October 2, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI189937.
Copyright © 2025, Cros et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published October 2, 2025 - Version history
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Abstract

Immune cells are constantly exposed to microbiota-derived compounds that can engage innate recognition receptors. How this constitutive stimulation is down-modulated to avoid systemic inflammation and auto-immunity is poorly understood. Here we show that Aryl hydrocarbon Receptor (AhR) deficiency in monocytes unleashes spontaneous cytokine responses in vivo, driven by 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 evidence an essential role for AhR in monocytes in restraining tonic microbiota sensing and in maintaining immune homeostasis.

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  • Version 1 (October 2, 2025): In-Press Preview
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