A tryptophan metabolite of the skin microbiota attenuates inflammation in patients with atopic dermatitis through the aryl hydrocarbon receptor

Abstract

TSLP AhR IAId Tryptophan Epidermis Dermis AhRE TSLP IL-4,IL-5,IL-13,IL-22AD Background: Previous studies have revealed significant alterations in the skin microbiota of patients with atopic dermatitis (AD) not only in diversity and composition but also in function, and the tryptophan (Trp) metabolic pathway is attenuated in the skin microbiota of patients with AD. Objective: We sought to assess Trp metabolites on the skin surfaces of patients with AD and to explore the function of the microbial Trp metabolites in skin inflammation in patients with AD.Methods: A gel-patch method was developed to collect metabolites on the skin surface, which were then assessed by using liquid chromatography-tandem mass spectrometry. A mouse model of calcipotriol (MC903)-induced AD-like dermatitis was used to evaluate the effects of microbial metabolites on AD, and aryl hydrocarbon receptor (AhR)-null mice and keratinocyte cultures were used to investigate the mechanism.We thank Professor Shau-Ku Huang for helpful suggestions and reviewing the manuscript. Key messagesd Levels of microbial metabolites of Trp metabolism on skin surfaces of patients with AD were lower than those of healthy subjects.d IAId significantly attenuated skin inflammation in a mouse model of MC903-induced AD-like dermatitis.d IAId inhibited TSLP expression in keratinocytes in an AhR-dependent manner.

Gut Microbial Catabolites of Tryptophan Are Ligands and Agonists of the Aryl Hydrocarbon Receptor: A Detailed Characterization

“…Previously, Zelante et al reported a vigorous agonist activity of IA in mouse H1L1.1c2 reporter cells [26]. Yu et al have demonstrated that IA attenuates inflammation in patients with atopic dermatitis through the AhR; however, direct evidence for IA effects on AhR has not been presented in that study [31].…”

“…These include photo-reactive Trp catabolites formed in the skin after irradiation by UV light [19], endogenous Trp metabolites [28], or microbial metabolites produced in the skin [31] or intestines [2,23]. Several (individual) Trp metabolites were studied in vitro for their AhR-mediated activities, but also in vivo, thus unveiling their potential physiological and pathological roles dependent on the AhR activation [17,26,27,31]. Nevertheless, a comprehensive study, describing the complex effects of the entire human or microbial Trp metabolome on the AhR has not been conducted so far.…”

Air Pollution and Atopic Dermatitis (AD): The Impact of Particulate Matter (PM10) on an AD Mouse-Model

“…Xenobiotic small chemicals have strong affinity to AHR and cause persistent activation of the receptor [ 28 ]. The pathogenic implication of AHR and its gene polymorphism in AD remain elusive but it has been suggested that most AHRs lack physiological ligands in the Th2-prone milieu in AD [ 31 , 34 ].…”

Meeting Report of the 4th Annual Meeting of the Chinese Society for Investigative Dermatology: Reflections on the Rise of Cutaneous Biology Research in China

“…TSLP-induced allergic Th2/Th17 polarization likely depends on dectin-2emediated allergen sensitization and upregulation of Th2/Th17-related cytokines. Han et al, 2017;Li et al, 2019Liang et al, 2019;Sun et al, 2011;Yu et al, 2019;Leprosy Variants of genes in the NOD2-mediated signaling pathway are associated with susceptibility to infection with M. leprae. HLA-B*13:01 was associated with the development of the dapsone hypersensitivity syndrome.…”