Enhanced phenotype of calcipotriol-induced atopic dermatitis in filaggrin-deficient mice
Enhanced phenotype of calcipotriol-induced atopic dermatitis in filaggrin-deficient mice
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丝聚蛋白缺陷小鼠中卡泊三醇诱导的特应性皮炎的增强表型
DOI：
10.1096/fj.202002709r
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Wang Gang
中科院分区：
文献类型：
--
作者：
Xiao Chunying;Sun Zhongbin;Gao Jixin;Bai Yaxing;Zhang Chen;Pang Bingyu;Qiao Hongjiang;Fu Meng;Dang Erle;Wang Gang
丝聚蛋白功能受损（FLG）是特应性皮炎（AD）的主要易感因素。一些关于FLG缺陷（Flg−/−）小鼠的研究表明FLG在皮肤屏障和AD的发展中起着重要作用，但没有一项研究描述了Flg −/−小鼠与卡泊三醇（CPT）诱导的特应性皮炎的特征，这限制了对FLG功能的全面了解。本研究试图产生Flg −/−小鼠，并应用CPT产生AD样皮炎，用于体内分析FLG功能。将CPT涂抹于Flg −/−小鼠皮肤上，建立AD样皮炎小鼠模型。通过耳毛厚度、组织病理学、免疫荧光和细胞因子产生来评价病变炎症。同时应用粘多糖多硫酸酯（MPS）和神经酰胺观察治疗作用。结果表明，Flg −/−小鼠中CPT诱导的皮炎炎症比野生型（WT）小鼠更严重，表现为大体外观、耳厚度、炎性细胞浸润（肥大细胞和CD 3 +T细胞）和炎性细胞因子表达（白细胞介素（IL）-4，IL-6，IL-13和胸腺基质淋巴细胞生成素（TSLP））水平增加。润肤剂MPS和神经酰胺部分恢复了患有CPT诱导的AD样皮炎的Flg −/−小鼠的表皮功能，并减轻了皮肤炎症。目前的研究表明，皮肤屏障蛋白FLG在AD的发病机制中至关重要。此外，CPT inFlg−/−小鼠诱导的AD小鼠模型可用于寻找AD的药物靶点。
Impaired function of filaggrin (FLG) is a major predisposing factor for atopic dermatitis (AD). Several studies on FLG‐deficient (Flg−/−) mice have indicated an essential role for FLG in the skin barrier and the development of AD, but none of the studies have described the characteristics onFlg−/−mice with calcipotriol (CPT)‐induced atopic dermatitis, which restricts the comprehensive understanding of functions of FLG. The present study sought to generateFlg−/−mice and applied CPT to produce AD‐like dermatitis for in vivo analysis of the FLG functions. CPT was applied on the skin ofFlg−/−mice to establish the AD‐like dermatitis mouse model. The lesion inflammation was evaluated by gross ear thickness, histopathology, immunofluorescence, and cytokine production. Also, mucopolysaccharide polysulfate (MPS) and ceramide were used to observe the therapeutic function in this model. The results showed that the inflammation of CPT‐induced dermatitis inFlg−/−mice was more severer than that of wild‐type (WT) mice, as evident by the increased level of gross appearance, ear thickness, inflammatory cell infiltration (mast cells and CD3+T cells), and inflammatory cytokine expression (interleukin (IL)‐4, IL‐6, IL‐13, and thymic stromal lymphopoietin (TSLP)). The emollients MPS and ceramide partially restored the epidermal function and alleviated the skin inflammation inFlg−/−mice with CPT‐induced AD‐like dermatitis. The current study demonstrated that skin barrier protein FLG is critical in the pathogenesis of AD. Also, the AD mouse model induced by CPT inFlg−/−mice could be utilized to search for drug targets in AD.