Synoviolin is not a pathogenic factor for auto-inflammatory diseases
Synoviolin is not a pathogenic factor for auto-inflammatory diseases
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滑膜蛋白不是自身炎症性疾病的致病因素
DOI：
10.1016/j.bbrc.2021.04.093
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发表时间：
2021
影响因子：
3.1
通讯作者：
Miyamoto Takeshi
中科院分区：
文献类型：
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作者：
Matsumoto Tatsuaki;Sato Yuiko;Kobayashi Tami;Ito Eri;Soma Tomoya;Kimura Atsushi;Miyamoto Kana;Kobayashi Shu;Harato Kengo;Matsumoto Morio;Nakamura Masaya;Niki Yasuo;Miyamoto Takeshi
自身炎症综合征是一种罕见的疾病，其特征是关节炎和关节破坏，症状类似于但不同于类风湿性关节炎（RA）。虽然E3连接酶Synoviolin先前被证明是RA的新治疗靶点，但尚未很好地表征自身炎症综合征的治疗靶点。在这里，我们表明，滑膜蛋白的损失对自身炎症性疾病的模型几乎没有影响。我们以前建立了这样一个模型，hIL-1 cTg小鼠，其中IL-1信号被组成性激活，动物表现出症状重演自身炎症综合征，如主要关节显性关节炎。在此，我们将hIL-1 cTg与Synoviolin flox'd小鼠杂交以产生hIL-1 cTg/Synoviolin cKO小鼠。通过注射pIpC以激活Mx 1启动子驱动的Cre重组酶，来消除成年hIL-1 cTg/Synoviolin cKO小鼠中的Synoviolingene表达。然而，针对Synoviolin并没有缓解hIL-1 cTg小鼠中观察到的症状，例如关节炎和关节破坏，因此排除了Synoviolin作为自身炎症性疾病的治疗靶点的可能性。我们的研究结果表明，虽然相似，类风湿关节炎和自身炎症性疾病是不同的疾病，治疗策略应该有所不同。
Auto-inflammatory syndromes are rare diseases characterized by arthritis and joint destruction, symptoms similar to but distinct from rheumatoid arthritis (RA). Therapeutic targets have not been well characterized for auto-inflammatory syndromes, although the E3 ligase Synoviolin was previously shown to be a novel therapeutic target for RA. Here, we show that Synoviolin loss has little impact on a model of auto-inflammatory diseases. We previously established such a model, the hIL-1 cTg mouse, in which IL-1 signaling was constitutively activated, and animals exhibit symptoms recapitulating auto-inflammatory syndromes such as major joint dominant arthritis. Here, we crossed hIL-1 cTg with Synoviolin flox’d mice to yield hIL-1 cTg/Synoviolin cKO mice.Synoviolingene expression was ablated in adult hIL-1 cTg/Synoviolin cKO mice by injection of pIpC to activate Mx1 promoter-driven Cre recombinase. However, symptoms seen in hIL-1 cTg mice such as arthritis and joint destruction were not alleviated by targeting Synoviolin, ruling out Synoviolin as a therapeutic target for auto-inflammatory disease. Our results indicate that although similar, RA and auto-inflammatory diseases are different diseases, and treatment strategies should differ accordingly.