Promoter demethylation contributes to TSLP overexpression in skin lesions of patients with atopic dermatitis

Abstract

Thymic stromal lymphopoietin (TSLP) plays an important role in promoting T-cell homeostasis, and appears to be a central player in the development of allergic symptoms, especially in asthma and atopic dermatitis (AD). Human TSLP is overexpressed in keratinocytes of patients with acute and chronic AD. However, the mechanism of TSLP overexpression remains unclear. To investigate whether TSLP expression is regulated by aberrant DNA methylation modification of the TSLP promoter in keratinocytes of patients with AD. mRNA and protein levels of TSLP in lesional skin samples from 10 children with AD and 10 healthy controls were measured by real-time quantitative reverse transcriptase-PCR and immunohistochemistry. Bisulfite sequencing was performed to determine the methylation status of the TSLP promoter, and 5-azacytidine (5-aza), a DNA methyltransferase inhibitor, was used to determine the influence of DNA methylation on TSLP expression. TSLP mRNA and protein expression levels were increased in skin lesions from patients with AD compared with healthy controls. Moreover, promoter hypomethylation of the TSLP gene was identified in skin lesions from patients with AD, and treating keratinocytes with 5-aza reduced the methylation level of the TSLP promoter and increased TSLP transcription. DNA demethylation of a specific regulatory region of the TSLP gene may contribute to TSLP overexpression in skin lesions in patients with AD.