Single-Cell Transcriptomic Characterization of DNCB-Induced Mouse Model Reveals Atopic Dermatitis-Associated Skin Lesions in Skin Microenvironment.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by complex cellular heterogeneity. While several studies have begun to characterize the single-cell transcriptomic landscape of human AD, comparable high-resolution data from widely used mouse models remain lacking. Here, we employed single-cell RNA sequencing to profile skin from a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model, which recapitulates key pathological features of human AD and is frequently used for mechanistic and therapeutic investigations. In this study, we identified 21 transcriptionally distinct clusters encompassing 11 major cell types. DNCB exposure resulted in robust immune infiltration, including Th2/Th17-skewed T cells, monocytes, macrophages, and inflamed endothelial cells. Keratinocytes were depleted and exhibited hyperproliferation, apoptosis, and differentiation defects, while novel fibroblast subsets displayed impaired maturation and pro-inflammatory states. Intercellular communication analysis revealed monocytes as dominant ligand-receptor signaling hubs. This study provides the first comprehensive single-cell atlas of the DNCB-induced AD model, revealing immune dysregulation, epithelial remodeling, and stromal reprogramming. Notably, the transcriptomic parallels with human AD validate the model’s translational relevance. Our findings establish a foundational reference for future AD research using the DNCB mouse model and offer valuable insights for interpreting drug and target discovery studies performed in this context. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10753-025-02391-5.