Over-expression of Truncated IK Ameliorates Dinitrochlorobenzene-Induced Allergic Contact Dermatitis Lesions in BALB/c Mice

截短型IK的过表达可减轻BALB/c小鼠二硝基氯苯诱导的过敏性接触性皮炎病变

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Abstract

BACKGROUND/AIM: Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity reaction mediated by hapten-specific T cells. Dinitrochlorobenzene (DNCB)-induced mouse models are widely used to investigate the pathogenesis of contact dermatitis. Inhibitor K562 (IK) cytokine suppresses IFN-γ-induced MHC class II expression on B cells by increasing cAMP levels. Previously, we reported that truncated IK (tIK) expression in transgenic (Tg) mice ameliorated rheumatoid arthritis by suppressing CD4(+) T helper cells (Th)-1 and Th17 cell differentiation, as well as macrophage activation. However, its role in hypersensitivity diseases such as ACD remains underexplored. This study aimed to evaluate whether tIK Tg mice exhibit reduced susceptibility to DNCB-induced ACD and passive systemic anaphylaxis (PSA). MATERIALS AND METHODS: ACD was induced in BALB/c and tIK Tg mice through repeated DNCB application. Ear thickness and scratching behavior were assessed. Serum IgE levels and mast cell-associated gene expression were analyzed. Th cell differentiation was evaluated using flow cytometry. PSA, an experimental model used to study systemic allergic reactions, was induced by IgE sensitization followed by antigen challenge, and hypothermia, serum IgE, and mast cell activation were measured. RESULTS: DNCB-treated BALB/c mice developed severe dermatitis, including increased ear thickness and scratching behavior, whereas tIK Tg mice exhibited milder symptoms. tIK over-expression also led to lower serum IgE levels and reduced mast cell-associated gene expression. T cell analysis revealed suppressed Th2 and Th17 differentiation, while Tregs and Th1 cells remained unaffected. Beyond ACD, tIK Tg mice exhibited attenuated PSA responses, with less severe hypothermia, lower serum IgE levels, and reduced mast cell activation compared to wild-type controls. CONCLUSION: tIK suppresses both localized and systemic hypersensitivity by modulating Th cell differentiation and mast cell activity. tIK may serve as a potential therapeutic target for allergic and inflammatory diseases.

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