Psoriatic inflammation facilitates the onset of arthritis in a mouse model.
Psoriatic inflammation facilitates the onset of arthritis in a mouse model.
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在小鼠模型中，银屑病炎症会促进关节炎的发作。
DOI：
10.1038/jid.2014.426
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Sano S
中科院分区：
文献类型：
--
作者：
Yamamoto M;Nakajima K;Takaishi M;Kitaba S;Magata Y;Kataoka S;Sano S
银屑病性关节炎（PsA）是一种血清阴性、与银屑病相关的炎性关节疾病。在大多数PsA患者中，皮肤病变先于关节炎;然而，皮肤炎症与关节炎发展的因果关系尚不清楚。Gp 130 F759/F759基因敲入（F759）小鼠在1岁后通过由于SOCS 3依赖性负调控受损而导致的持续信号转导子和转录激活子3（Stat 3）激活而发展自身免疫性关节炎。在这里，我们将F759小鼠与K5.Stat3C转基因小鼠杂交，其中角质形成细胞表达组成型活性Stat 3（Stat 3C），导致产生银屑病样皮肤变化。携带K5.Stat3C转基因的F759小鼠不仅有加重的皮肤损伤，而且早在3周龄时就在相邻爪中自发地发展出具有高转移率的关节炎。关节病变包括与皮肤病变相邻的外周爪肿胀和指甲畸形，与PsA非常相似。组织学检查显示附着点炎和骨侵蚀，伴有单核细胞浸润。定量逆转录酶-PCR（RT-PCR），免疫组化分析和流式细胞术显示在受影响的关节IL-23/辅助性T细胞17型（Th 17）通路的上调。此外，在F759小鼠中，通过用12-O-十四烷酰基佛波醇-13-乙酸酯（TPA）局部治疗来强制产生银屑病样皮肤炎症，诱导了下层关节的肿胀。该动物模型使银屑病炎症成为关节炎的驱动因素，有助于进一步了解PsA的发病机制。
Psoriatic arthritis (PsA) is a seronegative, inflammatory joint disease associated with psoriasis. In most patients with PsA, skin lesions precede arthritis; however, the causality of skin inflammation for the development of arthritis remains unclear. Gp130F759/F759knock-in (F759) mice develop autoimmune arthritis after 1 year of age through persistent signal transducer and activator of transcription 3 (Stat3) activation due to impairment in SOCS3-dependent negative regulation. Here, we crossed F759 mice with K5.Stat3C transgenic mice, in which keratinocytes express constitutive active Stat3 (Stat3C), leading to generation of psoriasis-like skin change. F759 mice harboring the K5.Stat3C transgene not only had aggravated skin lesions but also spontaneously developed arthritis with high penetrance in adjacent paws as early as 3 weeks of age. The joint lesions included swelling of the peripheral paws and nail deformities contiguous with the skin lesions, closely resembling PsA. Histopathologic study revealed enthesitis and bone erosions, with mononuclear cell infiltrates. Quantitative reverse transcriptase–PCR (RT–PCR), immunohistochemical analyses, and flow cytometry showed upregulation of the IL-23/T helper type 17 (Th17) pathway in affected joints. Furthermore, enforced generation of psoriasis-like skin inflammation by topical treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) in F759 mice induced swelling of the underlying joints. This animal model renders psoriatic inflammation as the driver of arthritis and helps to further understand the pathogenesis of PsA.