LB964 TET2 participates in the dysregulation of skin barrier in psoriasis

Psoriasis is a chronic inflammatory skin disease. Dysregulation of the epidermal barrier in psoriasis has been demonstrated and epigenetic modifications have found to be associated with psoriasis. TET2 dioxygenase activity oxidizes 5-methylcytosine (5mC) 5-hydroxymethylcytosine (5hmC), key regulator DNA demethylation. There lack studies on effect We observed reduced expression 5hmc lesions patients. In imiquimod psoriatic dermatitis mice, we obtained similar results by immunohistochemistry. constructed conditional knockout mice (TET2CKO). model, TET2CKO presented more severe erythema, scaling thickness. The TEWL assay was performed imiquimod-treated elevated group. This indicates that deficiency exacerbates mice. next examined K14, K10, filaggrin, involucrin, which represent proliferation differentiation, showed involucrin increased filaggrin decreased. absence may accelerate inhibit differentiation keratinocytes. subsequently intercellular linker molecules Claudin-1 E-cadherin were both downregulated conclusion, deletion involved dysregulation barrier. By RNAseq, FLG mRNA after knockdown. Deficiency encoded gene, leads impaired Filaggrin but mutations gene reported rarely psoriasis, therefore suppose might regulated TET2, an alternative mechanism for non-mutant