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Aryl hydrocarbon receptor (Ahr)-dependent Il-22 expression by type 3 innate lymphoid cells control of acute joint inflammation |
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| Authors: | Ramzi Nehmar Louis Fauconnier Jose Alves-Filho Dieudonnée Togbe Aurore DeCauwer Seiamak Bahram Marc Le Bert Bernhard Ryffel Philippe Georgel |
| Institution: | 1. Laboratoire d’ImmunoRhumatologie Moléculaire, Institut national de la santé et de la recherche médicale (INSERM) UMR_S 1109, Institut thématique interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Transplantex NG, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France
Contribution: Conceptualization (equal), Formal analysis (equal), Investigation (equal);2. ArtImmune SAS, Orleans, France Contribution: Investigation (equal);3. Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil Contribution: Investigation (equal);4. Laboratoire d’ImmunoRhumatologie Moléculaire, Institut national de la santé et de la recherche médicale (INSERM) UMR_S 1109, Institut thématique interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Transplantex NG, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France Contribution: Investigation (supporting), Methodology (supporting);5. Laboratoire d’ImmunoRhumatologie Moléculaire, Institut national de la santé et de la recherche médicale (INSERM) UMR_S 1109, Institut thématique interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Transplantex NG, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France Contribution: Funding acquisition (equal), Writing - original draft (equal);6. Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355, CNRS-University of Orléans, Orleans, France Contribution: Investigation (supporting);7. Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355, CNRS-University of Orléans, Orleans, France;8. Laboratoire d’ImmunoRhumatologie Moléculaire, Institut national de la santé et de la recherche médicale (INSERM) UMR_S 1109, Institut thématique interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Transplantex NG, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France |
| Abstract: | The aryl hydrocarbon receptor (AHR) controls several inflammatory and metabolic pathways involved in various diseases, including the development of arthritis. Here, we investigated the role of AHR activation in IL-22-dependent acute arthritis using the K/BxN serum transfer model. We observed an overall reduction of cytokine expression in Ahr-deficient mice, along with decreased signs of joint inflammation. Conversely, we report worsened arthritis symptoms in Il-22 deficient mice. Pharmacological stimulation of AHR with the agonist VAG539, as well as injection of recombinant IL-22, given prior arthritogenic triggering, attenuated inflammation and reduced joint destruction. The protective effect of VAG539 was abrogated in Il-22 deficient mice. Finally, conditional Ahr depletion of Rorc-expressing cells was sufficient to attenuate arthritis, thereby uncovering a previously unsuspected role of AHR in type 3 innate lymphoid cells during acute arthritis. |
| Keywords: | acute arthritis aryl hydrocarbon receptor IL-22 inflammation |