DNA methylation is an epigenetic modification that regulates gene transcription. DNA methyltransferase
1 (DNMT1) plays an important role in DNA methylation. However, the involvement of DNMT1 and DNA
methylation in the pathogenesis of atopic dermatitis (AD) remains unclear. In this study, microarray
analysis revealed that peripheral blood mononuclear cells of AD patients with low DNMT1 expression
(DNMT1-low) highly expressed dendritic cell (DC) activation-related genes. Also, DNMT1-low AD patients
exhibited a higher itch score compared to AD patients with high DNMT1 expression (DNMT1-high). By
using an AD-like mouse model induced by the application of Dermatophagoides farinae body ointment,
we found that Dnmt1 expression was decreased, while the expression of CeC chemokine receptor type 7
(Ccr7) was upregulated in mouse skin DCs. Furthermore, mice exposed to social defeat stress exhibited
Dnmt1 downregulation and Ccr7 upregulation in skin DCs. Additionally, dermatitis and itch-related
scratching behavior were exacerbated in AD mice exposed to stress. The relationship between low
DNMT1 and itch induction was found in both human AD patients and AD mice. In mouse bone marrowderived
DCs, Ccr7 expression was inhibited by 5-aza-2-deoxycytidine, a methylation inhibitor. Furthermore,
in mouse skin DCs, methylation of CpG sites in Ccr7 was modified by either AD induction or social
defeat stress. Collectively, these findings suggest that social defeat stress exacerbates AD pathology
through Dnmt1 downregulation and Ccr7 upregulation in mouse skin DCs. The data also suggest a role of
DNMT1 downregulation in the exacerbation of AD pathology.