Son Jehee, Oh Eun Young, Park Sohyun, Lee Sang-Myeong
Division of Biotechnology, College of Environmental and Bioresources, Jeonbuk National University, Iksan, Republic of Korea.
College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea.
In Vivo. 2025 May-Jun;39(3):1378-1393. doi: 10.21873/invivo.13941.
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).
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.
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.
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.
背景/目的：过敏性接触性皮炎（ACD）是一种由半抗原特异性T细胞介导的迟发型超敏反应。二硝基氯苯（DNCB）诱导的小鼠模型被广泛用于研究接触性皮炎的发病机制。抑制剂K562（IK）细胞因子通过提高cAMP水平抑制IFN-γ诱导的B细胞上MHC II类分子的表达。此前，我们报道转基因（Tg）小鼠中截短型IK（tIK）的表达通过抑制CD4辅助性T细胞（Th）-1和Th17细胞分化以及巨噬细胞活化改善了类风湿性关节炎。然而，其在诸如ACD等超敏性疾病中的作用仍未得到充分研究。本研究旨在评估tIK转基因小鼠对DNCB诱导的ACD和被动全身过敏反应（PSA）的易感性是否降低。
通过重复涂抹DNCB在BALB/c和tIK转基因小鼠中诱导ACD。评估耳部厚度和抓挠行为。分析血清IgE水平和肥大细胞相关基因表达。使用流式细胞术评估Th细胞分化。PSA是一种用于研究全身过敏反应的实验模型，通过IgE致敏然后进行抗原攻击诱导，测量体温过低、血清IgE和肥大细胞活化情况。
DNCB处理的BALB/c小鼠出现严重的皮炎，包括耳部厚度增加和抓挠行为，而tIK转基因小鼠表现出较轻的症状。tIK的过表达还导致血清IgE水平降低和肥大细胞相关基因表达减少。T细胞分析显示Th2和Th17分化受到抑制，而调节性T细胞（Tregs）和Th1细胞未受影响。除了ACD，tIK转基因小鼠的PSA反应减弱，与野生型对照相比，体温过低不那么严重，血清IgE水平较低，肥大细胞活化减少。
tIK通过调节Th细胞分化和肥大细胞活性抑制局部和全身超敏反应。tIK可能作为过敏性和炎性疾病的潜在治疗靶点。
