Immunobiology of Infection Unit, Institut Pasteur, INSERM U1221, Paris, France.
Université Paris 7, Sorbonne Paris Cité, Paris, France.
JCI Insight. 2020 Oct 15;5(20):140598. doi: 10.1172/jci.insight.140598.
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.
化脓性汗腺炎（HS）是一种病因不明的慢性皮肤疾病，表现为反复发作的疼痛性病变。皮肤微生态失调和未解决的炎症是活动性 HS 的标志，但它们的起源和相互作用仍不清楚。我们对 HS 皮肤的代谢组学分析显示，皮肤成纤维细胞中色氨酸分解的犬尿氨酸途径异常诱导，这与炎症细胞浸润释放犬尿氨酸途径诱导细胞因子有关。值得注意的是，病变皮肤中犬尿氨酸途径的过度激活与色氨酸的局部和全身耗竭有关。然而，皮肤微生物群通常会将宿主色氨酸降解为吲哚，通过芳基烃受体（AHR）的参与来调节组织炎症。在 HS 皮肤病变中，我们检测到 AHR 激活的上下文缺陷，同时伴有细菌衍生的 AHR 激动剂产生受损和驻留菌群中产生 AHR 配体的细菌减少。因此，皮肤微生物群界面处色氨酸分解代谢的失调为 HS 病变的免疫和微生物学特征提供了一种联系机制。除了揭示 HS 患者的代谢改变外，我们的研究还表明，纠正 AHR 信号传导有助于恢复 HS 皮肤的免疫稳态。
Zotero 插件
