Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 143, Issue 6, Pages 2108-+Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2018.11.036
Keywords
Atopic dermatitis; skin; microbiota; tryptophan; metabolites; indole-3-aldehyde; aryl hydrocarbon receptor; thymic stromal lymphopoietin
Categories
Funding
- National Natural Science Foundation of China [81573038, 91642116, 81573045, 31400782]
- CAMS Innovation Fund for Medical Sciences [2016-I2M-1-005]
- Natural Science Foundation of Jiangsu Province [BK20151066, BK20170162]
- Milstein Medical Asian American Partnership Foundation
- Municipal Human Resources Development Program for Outstanding Leaders in Medical Disciplines in Shanghai [2017BR039]
Ask authors/readers for more resources
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 assessTrpmetabolites on the skin surfaces of patients withADand to explore the function of the microbialTrp 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. Results: Major microbial metabolites of Trp were detected on the skin surfaces of healthy subjects, and the level of indole-3-aldehyde (IAId), an indole derivative of Trp catabolism, was significantly lower in lesional and nonlesional skin of patients with AD than that of healthy subjects. IAId significantly attenuated skin inflammation in mice with MC903-induced AD-like dermatitis, and this effect was blocked by an AhR antagonist and abolished in AhR-null mice. Furthermore, IAId was found to inhibit the MC903-induced expression of thymic stromal lymphopoietin in keratinocytes in vivo and in vitro, which was mediated by binding of AhR to the thymic stromal lymphopoietin promoter. Conclusion: IAId, a skin microbiota-derived Trp metabolite, negatively regulated skin inflammation in patients with AD, revealing that skin microbiota play a significant functional role in the pathogenesis of AD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available