CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands (original) (raw)

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Acknowledgements

We thank the members of the ANAXEM germ-free platform, the members of the animal facilities of INRA, and T. Ledent of the animal facilities of Saint-Antoine Hospital for their assistance in mouse care; M. Moroldo and J. Lecardonnel from the CRB GADIE core facility for technical assistance in performing the microarray analyses; S. Dumont for technical help in histology and immunochemistry; and C. Aubry, N.M. Breyner, F. Chain, S. Le Guin, C. Cherbuy, N. Lapaque, and D. Skurnik for fruitful discussions and technical help. We also thank E. Drouet and the Clinical Research Assistant team of Unité de Recherche Clinique de l'Est Parisien for their help in obtaining samples from patients with IBD. _Ido1_−/− and _Il22_−/− mice were provided by S. Taleb (INSERM Unit 970) and B. Ryffel (CNRS, UMR7355), respectively. The H1L1.1c2 cell line was provided by M.S. Denison (University of California, Davis). Funding was provided by Equipe ATIP–Avenir 2012 (H.S.), INSERM–ITMO SP 2013 (H.S.) and ECCO grant 2012 (H.S.).

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Authors and Affiliations

  1. Sorbonne University–Université Pierre et Marie Curie (UPMC), Paris, France
    Bruno Lamas, Valentin Leducq, Sarah Jegou, Loic Brot & Harry Sokol
  2. Institut National de la Santé et de la Recherche Médicale (INSERM) Equipe de Recherche Labélisée (ERL) 1157, Avenir Team Gut Microbiota and Immunity, Paris, France
    Bruno Lamas, Valentin Leducq, Sarah Jegou, Loic Brot & Harry Sokol
  3. Centre National de Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 7203, Paris, France
    Bruno Lamas, Valentin Leducq, Sarah Jegou, Loic Brot & Harry Sokol
  4. Laboratoire de BioMolécules (LBM), Centre Hospitalo-Universitaire (CHU) Saint-Antoine 27 rue de Chaligny, Paris, France
    Bruno Lamas, Valentin Leducq, Sarah Jegou, Loic Brot & Harry Sokol
  5. Micalis Institute, Institut National de la Recherche Agronomique (INRA), AgroParisTech, Université Paris–Saclay, Jouy-en-Josas, France
    Bruno Lamas, Mathias L Richard, Marie-Laure Michel, Gregory Da Costa, Chantal Bridonneau, Thomas W Hoffmann, Jane M Natividad, Philippe Langella & Harry Sokol
  6. Inflammation–Immunopathology–Biotherapy Department (DHU i2B), Paris, France
    Bruno Lamas, Mathias L Richard, Valentin Leducq, Marie-Laure Michel, Gregory Da Costa, Chantal Bridonneau, Sarah Jegou, Thomas W Hoffmann, Jane M Natividad, Loic Brot, Philippe Langella & Harry Sokol
  7. ILTOO Pharma, Incubateur et Pépinière d'Entreprises Paris–Salpêtrière, Hôpital Pitié Salpêtrière, Paris, France
    Hang-Phuong Pham
  8. INSERM U970, Paris Cardiovascular Research Center, Paris, France
    Soraya Taleb
  9. Université Paris-Descartes, Paris, France
    Soraya Taleb
  10. Laboratory of Experimental and Molecular Immunology and Neurogenetics, UMR 7355 CNRS–University of Orleans, Orleans, France
    Aurélie Couturier-Maillard & Bernhard Ryffel
  11. Department of Gastroenterology, Saint Antoine Hospital, Assistance Publique–Hopitaux de Paris, UPMC, Paris, France
    Isabelle Nion-Larmurier, Philippe Seksik, Anne Bourrier, Jacques Cosnes, Laurent Beaugerie & Harry Sokol
  12. INSERM, UMR S938, Centre de Recherche Saint-Antoine, Plateforme Morphologie du Petit Animal, Paris, France
    Fatiha Merabtene
  13. Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town, Republic of South Africa
    Bernhard Ryffel
  14. Department of Biochemistry, INSERM, UMR S942, Lariboisière Hospital, Paris, France
    Jean-Marie Launay
  15. Centre for Biological Resources BB-0033-00064, Lariboisière Hospital, Paris, France
    Jean-Marie Launay
  16. Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard University, Cambridge, Massachusetts, USA
    Ramnik J Xavier
  17. Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Ramnik J Xavier
  18. Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Ramnik J Xavier
  19. Center for Microbiome Informatics and Therapeutics, MIT, Cambridge, Massachusetts, USA
    Ramnik J Xavier

Authors

  1. Bruno Lamas
  2. Mathias L Richard
  3. Valentin Leducq
  4. Hang-Phuong Pham
  5. Marie-Laure Michel
  6. Gregory Da Costa
  7. Chantal Bridonneau
  8. Sarah Jegou
  9. Thomas W Hoffmann
  10. Jane M Natividad
  11. Loic Brot
  12. Soraya Taleb
  13. Aurélie Couturier-Maillard
  14. Isabelle Nion-Larmurier
  15. Fatiha Merabtene
  16. Philippe Seksik
  17. Anne Bourrier
  18. Jacques Cosnes
  19. Bernhard Ryffel
  20. Laurent Beaugerie
  21. Jean-Marie Launay
  22. Philippe Langella
  23. Ramnik J Xavier
  24. Harry Sokol

Contributions

B.L., M.L.R., and H.S. conceived and designed the study, performed data analysis, and wrote the manuscript; B.L. designed and conducted all experiments, unless otherwise indicated; V.L. designed and performed the AHR activity experiments; G.D.C., C.B., S.J., T.W.H., J.M.N., L. Brot, F.M., and M.-L.M. provided technical help for the in vitro and in vivo experiments; H.-P.P. conducted the bioinformatics studies and analyzed the microarray experiments; J.-M.L. performed and analyzed HPLC experiments; S.T. provided material from the _Ido1_−/− mice and discussed the results; A.C.-M. and B.R. provided material from the _Il22_−/− mice and discussed the results; H.S., J.C., I.N.-L., A.B., L. Beaugerie, and P.S. provided data and samples for the patients with IBD; B.L., M.L.R., R.J.X., P.L., and H.S. discussed the experiments and results.

Corresponding author

Correspondence toHarry Sokol.

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The authors declare no competing financial interests.

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Lamas, B., Richard, M., Leducq, V. et al. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands.Nat Med 22, 598–605 (2016). https://doi.org/10.1038/nm.4102

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