Profiling transcriptomic changes and signaling pathways in atopic dermatitis by integrative analyses on multiple databases

Atopic dermatitis (AD) is a condition driven by T cell-mediated immune response. Targeted therapy of AD is challenging due to its complex pathogenesis. In the current study, by analyzing multiple expression and network datasets, we aimed at: (1) identifying important transcriptomic signatures/profiles for AD to seek potential therapeutic targets and (2) discovering key regulators in the pathogenesis of AD. Our differentially expressed gene (DEG) analysis revealed multiple genes involved in immune response and dermal structural integrity. Functional enrichment analyses suggested that signaling pathways involved in epidermal barrier and inflammation and immunity are overrepresented in lesional AD. Protein-protein interaction (PPI) network and causal interactions analyses highlighted the roles of regulators of epidermal integrity and immune response in the pathogenesis of AD. Prominently, a negative regulator of the B-cell receptor-mediated immune response, PKC beta, has been suggested in the predicted pathogenesis model for AD, implying B cell-mediated immune response may play an equally important role as that of the T cell-mediated immune response in AD. A further search in a perturbagen database has identified small molecular drugs that may alter expression profiles of key regulators in the pathogenesis of AD. In this study, we propose a systemic multi-omics strategy incorporating multiple analyses on various datasets of transcriptomes, diseases, and pharmacology. Such integrative analyses will effectively advance our understanding on the pathogenesis and treatment of AD.

Automated summary

In this study, various datasets were analyzed to identify transcriptomic signatures and key regulators of atopic dermatitis (AD). The results revealed genes related to immune response and dermal integrity, overrepresented signaling pathways in lesional AD, and the roles of regulators in epidermal integrity and immune response. The study also suggested a potential role of B cell-mediated immune response in the pathogenesis of AD, in addition to the well-known T cell-mediated immune response. Furthermore, small molecular drugs were identified as potential therapeutic targets for AD based on the analysis.