Publication date: Available online 20 December 2018
Source: Journal of Allergy and Clinical Immunology
Author(s): Jinlei Yu, Yang Luo, Zhenlai Zhu, Yufeng Zhou, Licheng Sun, Jixin Gao, Jinlv Sun, Gang Wang, Xu Yao, Wei Li
Abstract
Background
Previous studies have revealed significant alterations in the skin microbiota of AD patients not only in diversity and composition but also in function, and the tryptophan (Trp) metabolic pathway is attenuated in the skin microbiota of AD patients.
Objective
To assess Trp metabolites on the skin surface of AD patients and to explore the function of the microbial Trp metabolites in skin inflammation in AD.
Methods
A gel-patch method was developed to collect metabolites on the skin surface, which were then assessed by liquid chromatography-mass spectrometry/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 culture were utilized to investigate the mechanism.
Results
Major microbial metabolites of Trp were detected on the skin surface of healthy individuals, and the level of indole-3-aldehyde (IAId), an indole derivative of Trp catabolism, was significantly lower in lesional and non-lesional skin of AD patients than that of healthy individuals. IAId significantly attenuated the skin inflammation in MC903-induced AD-like dermatitis, and this effect was blocked by an AhR antagonist and abolished in AhR-null mice. Further, IAId was found to inhibit the MC903-induced expression of thymic stromal lymphopoietin (TSLP) in keratinocytes in vivo and in vitro, which was mediated by the binding of AhR to the TSLP promoter.
Conclusion
IAId, a skin microbiota-derived tryptophan metabolite, negatively regulated skin inflammation in AD, revealing that the skin microbiota play a significant functional role in the pathogenesis of AD.
Graphical abstract
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