IL-4, IL-13, TNF-α and IFN-γ Downregulate CLDN8 Expression Through Activating JAK Signaling Pathway in HaCaT Cells

Xiaojie Wang,* Dandan Mao,* Zhanglei Mu Department of Dermatology, Peking University People’s Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhanglei Mu, Department of Dermatology, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Email [email protected]: Tight junctions (TJs) are important for skin barrier function. Claudin-8 (CLDN8), a member of TJs, was indicated decreased in several RNA sequencing studies in dermatitis conditions.Methods: Bioinformatics analysis was performed to extract CLDN8 mRNA expression from atopic dermatitis (AD) related datasets in the Gene Expression Omnibus. CLDN8 protein expression was detected in AD lesions and healthy control skin tissues using immunohistochemistry staining (IHC). Cldn8 expression was detected in MC903-induced AD-like mouse model. AD-related cytokines with or without Janus kinase (JAK) inhibitor were added to HaCaT cells, and CLDN8 expression was detected by quantitative Polymerase Chain Reaction (qPCR).Results: CLDN8 mRNA expression is decreased in AD lesions and MC903-induced AD-like mouse model. Downregulation of CLDN8 mRNA expression is alleviated after dupilumab or crisaborole treatment. CLDN8 protein was not detected by IHC in human or mouse skin tissues. Interleukin (IL)-4, IL-13, tumor necrosis factor (TNF)-α and interferon (IFN)-γ downregulated CLDN8 mRNA expression in HaCaT cells through activating JAK.Conclusion: CLDN8 mRNA is decreased in AD lesions, and the decreased CLDN8 is alleviated along with therapy. Skin tissues might not express CLDN8 protein. AD-related cytokines including IL-4, IL-13, TNF-α and IFN-γ could downregulate CLDN8 mRNA expression through activating JAK.Keywords: claudin-8, tight junction, atopic dermatitis, Janus kinase