956 Epidermal keratinocyte-specific STAT3 deficiency aggravated atopic dermatitis-like skin inflammation in mice through TSLP upregulation

Atopic dermatitis (AD) is a common inflammatory skin disorder with complex pathogenesis, involving epidermal barrier dysfunction, microbiome abnormalities and type-2-skewed immune dysregulation. The signal transducer activator of transcription 3 (STAT3) factor which plays critical roles in variety biological processes. However, the role STAT3 keratinocytes AD remains unclear. In this study, we generated an keratinocyte-specific Stat3-deficient mouse strain (termed Stat3 cKO mice). By using topical 2,4-dinitrochlorobenzene (DNCB), mice developed worsened AD-like dermatitis, manifested as thickening swelling ear accompanied by exudation crusting. number Ki67-positive cells was significantly increased upregulation K14 expression mice, but barrier-related proteins (Loricrin, Filaggrin) antimicrobial peptides (S100A9, LL37, β-defensin 2) were downregulated. Moreover, dominant microbial population changed from Ralstonia to Staphylococcus, determined Pacbio full-length 16s rRNA sequencing. addition, displayed more CD4+T p-STAT6-positive level type 2 cytokine IL-4 after DNCB induction. Furthermore, thymic stromal lymphopoietin (TSLP), mainly produced keratinocytes, highly expressed could chemoattract TSLPR-positive cells. Inhibition TSLP subcutaneous injection monoclonal antibody alleviated mice. Thus, deficiency aggravate inflammation its key may be dysregulated TSLP.