IL-32 promotes the occurrence of atopic dermatitis by activating the JAK1/microRNA-155 axis

Abstract

Background This study aims to explore the mechanism of interleukin-32 (IL-32) affecting atopic dermatitis (AD) through the Janus-activated kinase-1 (JAK1)/microRNA-155 (miR-155) axis. Methods In this study, skin tissue samples and blood samples from normal subjects and patients with AD, human immortalized keratinocytes (HaCaT), and PA-induced mouse models of AD were selected for expression determination of IL-32, JAK1 and miR-155. The interaction among IL-32, JAK1 and miR-155 was identified with their roles in AD analyzed through loss- and gain-of-function assays. Results Elevated IL-32 was detected in AD tissues and blood samples and promoted the occurrence of AD. IL-32 upregulated JAK1 expression and phosphorylation of its downstream genes, thus activating the JAK signaling pathway. JAK1 promoted the expression of miR-155. IL-32/JAK1/miR-155 axis promoted inflammation in the AD skin reconstruction model. In vivo experiments further confirmed that IL-32 promoted AD development by activating the JAK1/miR-155 axis. Conclusion The present study underlined that IL-32 promoted the occurrence of AD by promoting JAK1 expression to upregulate miR-155 expression.

IL-32 as a potential biomarker and therapeutic target in skin inflammation

“…Another study showed that IL-32 promotes AD through JAK-miRNA-155 signalling ( 8 ). In this study, the expression of IL-32 in skin and blood samples was higher in AD than in healthy control samples, both in an IL-32 transgenic murine AD model induced by phthalic anhydride (PA) and in human patients.…”

“…Lesional skin of AD patients was found to have increased levels of IL-32 ( 7 ). In addition, IL-32 serum levels of AD patients were shown to be increased and correlated with disease severity ( 7 , 8 ). Treatment with oral cyclosporin for 28 days was found to decrease IL-32 levels in the serum of AD patients, which was accompanied by an alleviation of skin lesions in these patients ( 9 ).…”

Intrinsic Effects of Exposome in Atopic Dermatitis: Genomics, Epigenomics and Regulatory Layers

“…Despite the inherent differences and opposing underlying mechanisms between lesional skin and peripheral blood cells during inflammation, the pivotal regulators of inflammation, such as miR-146a , mir-223, and miR-155, persist in an upregulated profile in eczema biopsies [ 60 , 66 , 77 , 78 , 79 , 80 ]. However, Sonkoly et al proved that skin-resident immune cells, particularly CD4+ CD3+ T cells, are responsible for the enhanced mir-155 signals in AD skin biopsies through immunohistochemical staining [ 81 ].…”

Identification of potential miR‑155 target genes in epidermal immune microenvironment of atopic dermatitis patients and their inflammatory effects on HaCaT cells

“…miR-155 is expressed by cutaneous T cells, dendritic cells and mast cells. Previously studies have shown that miR-155 is overexpressed in patients with AD, such that it is the most significantly upregulated microRNA in terms of expressions ( 9 , 10 ). It can enhance T cell proliferation by inhibiting cytotoxic T lymphocyte associated antigen-4 (CTLA-4) ( 11 ).…”

“…In AD mouse models, miR-155 has been shown to target cAMP-dependent protein kinase inhibitor α and regulate tight junction protein expression, which in turn affect epithelial barrier function ( 10 ). In the skin model of AD, IL-32 has been reported to promote the expression of Janus kinase 1 and upregulate miR-155 expression, leading to the occurrence of AD inflammation ( 9 ). Although evidence on the role of miR-155 in the pathogenesis of AD has been accumulating, the mechanism of miR-155 underlying the development of AD remains unclear and requires further research.…”