Background: Atopic dermatitis (AD) is a chronic inflammatory disease characterized by immune dysregulation and skin barrier dysfunction. Recent evidence suggests that the monocyte chemotactic protein-1 (MCP-1)/C-C motif chemokine receptor 2 (CCR2) signaling pathway plays a crucial role in the recruitment of inflammatory cells and immune activation. This study aimed to investigate the role and underlying mechanisms of the MCP-1/CCR2 signaling pathway in AD pathogenesis.

Methods: A 1-Chloro-2,4-dinitrobenzene (DNCB)-induced AD mouse model and in vitro HaCaT cell-based experiments were employed. Clinical skin lesion scores, transepidermal water loss (TEWL), scratching bouts, and visceral indices were assessed. Histopathological changes were evaluated via hematoxylin and eosin (H&E) staining. The expression levels of inflammatory cytokines, skin barrier proteins, and components of the MCP-1/CCR2 pathway were determined using enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot analyses. Furthermore, the MCP-1/CCR2 pathway was inhibited using Bindarit to evaluate its role in modulating inflammation and barrier function.

Results: AD mice exhibited severe skin lesions, with TEWL increased by ~3.5-fold (p < 0.05) and scratching bouts elevated by ~3-fold (p < 0.05) compared to controls. Serum levels of immunoglobulin E (IgE), interleukin (IL)-4, and IL-5 were significantly higher in AD mice than in controls (p < 0.05). Additionally, MCP-1 and its receptor CCR2 showed time-dependent upregulation at both the mRNA and protein levels (p < 0.05). Following Bindarit treatment, the expression levels of inflammation-related genes were significantly reduced (p < 0.05), and the levels of skin barrier-associated proteins tended to normalize.

Conclusion: The MCP-1/CCR2 signaling pathway contributes to AD pathogenesis by promoting inflammatory cell recruitment and activating downstream signaling, leading to skin barrier dysfunction. Targeted inhibition of this pathway may represent a promising therapeutic strategy for alleviating AD symptoms and restoring skin barrier integrity.