Dysregulation of tryptophan catabolism at the host-skin microbiota interface in hidradenitis suppurativa - Département d'immunologie Accéder directement au contenu
Article Dans Une Revue JCI Insight Année : 2020

Dysregulation of tryptophan catabolism at the host-skin microbiota interface in hidradenitis suppurativa

Jean-Marc Doisne
Pedro Goncalves
Darragh Duffy
Aude Nassif
James P. Di Santo

Résumé

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.

Domaines

Immunologie
Fichier principal
Vignette du fichier
140598.2-20201007112112-covered-253bed37ca4c1ab43d105aefdf7b5536.pdf (6.78 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

pasteur-02983317 , version 1 (29-10-2020)

Licence

Paternité

Identifiants

Citer

Laure Guenin-Macé, Jean-David Morel, Jean-Marc Doisne, Angèle Schiavo, Lysiane Boulet, et al.. Dysregulation of tryptophan catabolism at the host-skin microbiota interface in hidradenitis suppurativa. JCI Insight, 2020, 5 (20), pp.e140598. ⟨10.1172/jci.insight.140598⟩. ⟨pasteur-02983317⟩
64 Consultations
94 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More