Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, China.
Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, China.
J Dermatol Sci. 2024 Jun;114(3):104-114. doi: 10.1016/j.jdermsci.2024.05.003. Epub 2024 May 18.
Although several mouse models of exogenous-agent-induced atopic dermatitis (AD) are currently available, the lack of certainty regarding their similarity with human AD has limited their scientific value. Thus, comprehensive evaluation of the characteristics of mouse models and their similarity with human AD is essential.
To compare six different exogenous-agent-induced AD mouse models and find out the optimum models for study.
Female BALB/c mice underwent induction of AD-like dermatitis by MC903 alone or in combination with ovalbumin (OVA), dinitrofluorobenzene (DNFB) alone or in combination with OVA, OVA alone, or Staphylococcus aureus. Gross phenotype, total immunoglobulin E (IgE) level, histopathological manifestations, and skin lesion transcriptome were analyzed, and metagenomic sequencing of the gut microbiome was performed.
The DNFB plus OVA model showed the highest disease severity, while the OVA model showed the lowest severity. The MC903 and MC903 plus OVA models showed high expression of T-helper (Th)2- and Th17-related genes; the DNFB and DNFB plus OVA models showed upregulation of Th1-, Th2-, and Th17-related genes; while the S. aureus inoculation model showed more enhanced Th1 and Th17 immune responses. In contrast to the other models, the OVA-induced model showed the lowest expression levels of inflammation-related genes, while the MC903 model shared the largest overlap with human AD profiles. The intestinal microbiota of all groups showed significant differences after modeling.
Each AD mouse model exhibited different characteristics. The MC903 model was the best to recapitulate most features of human AD among these exogenous-agent-induced AD models.
虽然目前有几种外源性物质诱导的特应性皮炎（AD）的小鼠模型，但由于它们与人类 AD 的相似性存在不确定性，限制了其科学价值。因此，全面评估小鼠模型的特征及其与人类 AD 的相似性至关重要。
比较 6 种不同外源性物质诱导的 AD 小鼠模型，寻找最佳的研究模型。
雌性 BALB/c 小鼠单独或联合卵清蛋白（OVA）、二硝基氟苯（DNFB）、OVA 或金黄色葡萄球菌诱导 AD 样皮炎。分析大体表型、总免疫球蛋白 E（IgE）水平、组织病理学表现和皮肤病变转录组，并进行肠道微生物组的宏基因组测序。
DNFB 联合 OVA 模型疾病严重程度最高，而 OVA 模型严重程度最低。MC903 和 MC903 联合 OVA 模型显示 Th2 和 Th17 相关基因高表达；DNFB 和 DNFB 联合 OVA 模型显示 Th1、Th2 和 Th17 相关基因上调；而金黄色葡萄球菌接种模型显示增强的 Th1 和 Th17 免疫反应。与其他模型相比，OVA 诱导的模型显示炎症相关基因表达水平最低，而 MC903 模型与人类 AD 谱的重叠最大。建模后所有组的肠道微生物群均显示出显著差异。
每种 AD 小鼠模型均表现出不同的特征。在这些外源性物质诱导的 AD 模型中，MC903 模型最能重现人类 AD 的大多数特征。
