Dysregulation of tryptophan catabolism at the host-skin microbiota interface in Hidradenitis Suppurativa
| العنوان: | Dysregulation of tryptophan catabolism at the host-skin microbiota interface in Hidradenitis Suppurativa |
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| المؤلفون: | Jean-Marc Doisne, Pedro Gonçalves, Lysiane Boulet, Marie-Noëlle Ungeheuer, Laure Guenin-Macé, Sabine Duchatelet, Vincent Bondet, James P. Di Santo, Alain Hovnanian, Aude Nassif, Darragh Duffy, Maïa Delage, Angèle Schiavo, Véronique Mayau, J Morel, Caroline Demangel |
| المساهمون: | Immunobiologie de l'Infection - Immunobiology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (USPC), École normale supérieure de Lyon (ENS de Lyon), Immunité Innée - Innate Immunity, Biochimie Hormonale et Nutritionnelle, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Genetic skin diseases : from disease mechanism to therapies (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunobiologie des Cellules dendritiques, Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Institut Pasteur [Paris] (IP), Centre Médical de l'Institut Pasteur (CMIP), This study was supported by Institut Pasteur (to CD and JPDS) via the Center for Translational Science, INSERM (U1221, to CD, U1223, to JPDS), and 'Société Française de Dermatologie' (to AN). The Biomics Platform, C2RT, Institut Pasteur is supported by France Génomique (ANR-10-INBS-09-09) and IBISA., We thank Armanda Casrouge for assistance in performing the immunostaining of skin biopsies, Olivier Join-Lambert for fruitful discussions on the skin microbiota of patients with HS, and Harry Sokol for his critical reading of this manuscript. We also thank Valérie Briolat and Laurence Motreff of the Biomics Wet-Lab Platform for 16S rRNA sequencing and the Image Analysis Hub for immunofluorescence data processing., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], École normale supérieure - Lyon (ENS Lyon), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Pasteur [Paris], Centre Médical de l'Institut Pasteur, Vougny, Marie-Christine, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| المصدر: | JCI Insight JCI Insight, 2020, 5 (20), pp.e140598. ⟨10.1172/jci.insight.140598⟩ JCI Insight, Vol 5, Iss 20 (2020) JCI Insight, American Society for Clinical Investigation, 2020, 5 (20), pp.e140598. ⟨10.1172/jci.insight.140598⟩ |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Kynurenine pathway, chemistry.chemical_compound, 030207 dermatology & venereal diseases, 0302 clinical medicine, Hidradenitis suppurativa, Immune homeostasis, Kynurenine, Skin, 0303 health sciences, integumentary system, biology, Tryptophan, General Medicine, Middle Aged, Hidradenitis Suppurativa, 3. Good health, 030220 oncology & carcinogenesis, Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, Research Article, Adult, [SDV.IMM] Life Sciences [q-bio]/Immunology, Inflammation, Dermatology, Amino acid metabolism, Tryptophan catabolism, 03 medical and health sciences, medicine, Humans, 030304 developmental biology, Host Microbial Interactions, business.industry, Cellular immune response, Fibroblasts, medicine.disease, Aryl hydrocarbon receptor, Metabolism, 030104 developmental biology, Receptors, Aryl Hydrocarbon, chemistry, Axilla, Immunology, biology.protein, business, Dysbiosis |
| الوصف: | Hidradenitis suppurativa (HS) is a chronic skin disorder of unknown etiology that manifests as recurrent, painful lesions. Cutaneous dysbiosis and unresolved inflammation are hallmarks of active HS, but their origin and interplay remain unclear. Our metabolomic profiling of HS skin revealed an abnormal induction of the kynurenine pathway of tryptophan catabolism in dermal fibroblasts, correlating with the release of kynurenine pathway–inducing cytokines by inflammatory cell infiltrates. Notably, overactivation of the kynurenine pathway in lesional skin was associated with local and systemic depletion in tryptophan. Yet the skin microbiota normally degrades host tryptophan into indoles regulating tissue inflammation via engagement of the aryl hydrocarbon receptor (AHR). In HS skin lesions, we detected contextual defects in AHR activation coinciding with impaired production of bacteria-derived AHR agonists and decreased incidence of AHR ligand-producing bacteria in the resident flora. Dysregulation of tryptophan catabolism at the skin-microbiota interface thus provides a mechanism linking the immunological and microbiological features of HS lesions. In addition to revealing metabolic alterations in patients with HS, our study suggests that correcting AHR signaling would help restore immune homeostasis in HS skin. Loss of homeostasis of tryptophan metabolism at the host-microbiota interface may contribute to Hidradenitis Suppurativa. |
| وصف الملف: | application/pdf |
| تدمد: | 2379-3708 |
| DOI: | 10.1101/2020.08.25.20181438 |
| DOI: | 10.1172/jci.insight.140598⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4025934de5b782576f824af5259b546b https://doi.org/10.1101/2020.08.25.20181438 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4025934de5b782576f824af5259b546b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23793708 |
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| DOI: | 10.1101/2020.08.25.20181438 |