Establishment of a Mouse Model of Atopic Dermatitis by Deleting Ikk2 in Dermal Fibroblasts
Establishment of a Mouse Model of Atopic Dermatitis by Deleting Ikk2 in Dermal Fibroblasts
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DOI：
10.1016/j.jid.2018.10.047
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发表时间：
2019-06-01
影响因子：
6.5
通讯作者：
Kitajima, Isao
中科院分区：
文献类型：
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作者：
Nunomura, Satoshi;Ejiri, Naoko;Kitajima, Isao
特应性皮炎是一种慢性炎症性皮肤病，伴有持续性瘙痒。为了阐明其分子机制，建立与特应性皮炎患者表型相似的小鼠模型，特别是在表现抓挠行为方面。Ikk2是I κ B激酶复合物的一种成分，可产生促炎反应，而其在角质形成细胞中的缺乏却矛盾地引起皮肤炎症。在这项研究中，我们试图建立一个皮肤成纤维细胞缺乏Ikk2表达的皮肤炎症小鼠模型，并评估皮肤炎症表型是否与特应性皮炎患者相似。生成ikk2缺陷小鼠(Nestin(cre)；Ikk2(FL/FL))在真皮成纤维细胞中缺失，我们将雌性Ikk2（FL/FL）小鼠与雄性Nestin（cre）杂交；Ikk2 (FL / +)老鼠。这些小鼠自发发展为仅限于面部的皮肤炎症，面部皮肤出现ikk2缺陷成纤维细胞。这些小鼠表现出与特应性皮炎患者相似的表型，包括抓挠行为，这些行为对免疫抑制剂或分子靶向药物具有抗性。这些发现提示巢蛋白（cre）；Ikk2（FL/FL）小鼠是一种特应性皮炎模型，它将有助于阐明特应性皮炎的发病机制和开发治疗特应性皮炎症状的新药物。
Atopic dermatitis is a chronic inflammatory skin disease with persistent pruritus. To clarify its molecular mechanism, it is important to establish a mouse model similar to the phenotypes of atopic dermatitis patients, particularly in exhibiting scratching behavior. Ikk2, a component of the I kappa B kinase complex, exerts proinflammatory responses, whereas its deficiency in keratinocytes paradoxically causes skin inflammation. In this study, we sought to generate a mouse model exhibiting skin inflammation by which dermal fibroblasts lack Ikk2 expression and evaluate whether cutaneous inflammatory phenotypes are similar to those of atopic dermatitis patients. To generate Ikk2-deficient mice (Nestin(cre); Ikk2(FL/FL)) in which Ikk2 is deleted in dermal fibroblasts, we crossed female Ikk2(FL/FL) mice to male Nestin(cre); Ikk2(FL/+) mice. These mice spontaneously developed skin inflammation limited to the face, with the appearance of Ikk2-deficient fibroblasts in the facial skin. These mice showed phenotypes similar to those of atopic dermatitis patients, including scratching behaviors, which are resistant to immunosuppressive or molecularly targeted drugs. These findings suggest that the Nestin(cre); Ikk2(FL/FL) mouse is an atopic dermatitis model that will be useful in clarifying atopic dermatitis pathogenesis and in developing a novel therapeutic agent for atopic dermatitis symptoms.