Skip to Main content Skip to Navigation
Journal articles

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

Abstract : 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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [58 references]  Display  Hide  Download

https://hal-pasteur.archives-ouvertes.fr/pasteur-02983317
Contributor : Marie-Christine Vougny <>
Submitted on : Thursday, October 29, 2020 - 4:19:20 PM
Last modification on : Thursday, November 19, 2020 - 8:27:32 AM

File

140598.2-20201007112112-covere...
Publication funded by an institution

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Citation

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, American Society for Clinical Investigation, 2020, 5 (20), pp.e140598. ⟨10.1172/jci.insight.140598⟩. ⟨pasteur-02983317⟩

Share

Metrics

Record views

23

Files downloads

88