Microbial dysbiosis in the skin has been implicated in the pathogenesis of atopic dermatitis (AD); however, whether and how changes in the skin microbiome initiate skin inflammation, or vice versa, remains poorly understood. Here, we report that the levels of sebum and its microbial metabolite, propionate, were lower on the skin surface of AD patients compared with those of healthy individuals. Topical propionate application attenuated skin inflammation in mice with MC903-induced AD-like dermatitis by inhibiting IL-33 production in keratinocytes, an effect that was mediated through inhibition of HDAC and regulation of the AhR signaling pathway. Mice lacking sebum spontaneously developed AD-like dermatitis, which was improved by topical propionate application. A proof-of-concept clinical study further demonstrated the beneficial therapeutic effects of topical propionate application in AD patients. In summary, we have uncovered that the dysregulated sebum–microbial metabolite–IL-33 axis might play an initiating role in AD-related skin inflammation, thereby highlighting novel therapeutic strategies for the treatment of AD.

Atopic dermatitis (AD) is recognized as a common inflammatory skin disease and frequently occurred in Asian and Black individuals. Since the limitation of dataset associated with human severe AD, this study aimed to screen potential novel biomarkers involved in mild AD. Expression profile data (GSE75890) were obtained from the database of Gene Expression Omnibus. Using limma package, the differentially expressed genes (DEGs) between samples from AD and healthy control were selected. Furthermore, function analysis was conducted. Meanwhile, the protein-protein interaction (PPI) network and transcription factor (TF)-miRNA-target regulatory network were constructed. And quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the expressions patterns of key genes. In total, 285 DEGs including 214 upregulated and 71 downregulated genes were identified between samples from two groups. The upregulated DEGs were mainly involved in nine pathways, such as hematopoietic cell lineage, pertussis, p53 signaling pathway, staphylococcus aureus infection, and cell cycle, while tight junction was the only pathway enriched by the downregulated DEGs. Cyclin B (CCNB)1, CCNB2, cyclin A (CCNA)2, C-X-C motif chemokine ligand (CXCL)10, and CXCL9 were key nodes in PPI network. The TF-miRNA-target gene regulatory network focused on miRNAs such as miR-106b, miR-106a, and miR-17, TFs such as nuclear factor kappa B subunit 1, RELA proto-oncogene, Sp1 transcription factor, and genes such as matrix metallopeptidase 9, peroxisome proliferator activated receptor gamma , and serpin family E member 1. Moreover, the upregulation of these genes, including CCNB1, CCNB2, CCNA2, CXCL10, and CXCL9 were confirmed by qRT-PCR. CCNB1, CCNB2, CCNA2, and CXCL9 might be novel markers of mild AD. miR-106b and miR-17 may involve in regulation of immune response in AD patients.

Background/Objective: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by diverse clinical manifestations. However, variations in its clinical presentations across different ages, genders, anatomical sites, and seasons remain incompletely understood. The objective was to explore the clinical heterogeneities of AD using data from the Chinese non-selective registration system. Methods: A prospective analysis was conducted on 3829 AD patients enrolled in the Chinese Non-selective Registry for AD (CNRAD) at hospital settings from 2020 to 2022. Demographic profiles; distribution, type, and severity of the skin lesion; laboratory findings; allergic comorbidities; family history; and exacerbating factors were analyzed. Results: The male-to-female ratio was 0.92 among adolescent and adult AD patients but increased to 2.11 in elderly AD patients, highlighting an age-dependent gender difference in AD prevalence. Age groups displayed distinct anatomical preferences for lesion distribution, with reduced involvement of the cubital and popliteal fossae in adult and elderly patients. Based on skin lesion characteristics, ten clinical subtypes of AD were proposed. Elderly AD patients exhibited higher severity, compared to adolescence and adult AD patients, with male patients being more severe than females. Elderly AD patients showed a lower proportion of extrinsic type, compared to childhood AD patients. Seasonal change emerged as the most important factor triggering AD flares. Conclusions: This study provides new insights into the heterogeneities of AD clinical manifestations in the Chinese population, demonstrating their significant dependence on temporal factors, including age and season.