Murine models of idiopathic inflammatory myopathy
Murine models of idiopathic inflammatory myopathy
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DOI：
10.1080/25785826.2022.2137968
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发表时间：
2022-10
影响因子：
4.4
通讯作者：
R. Konishi;Y. Ichimura;N. Okiyama
中科院分区：
文献类型：
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作者：
R. Konishi;Y. Ichimura;N. Okiyama
摘要特发性炎性肌病是以肌肉和其他器官的炎症为特征的疾病。几种肌炎特异性自身抗体（MSA）已在IIM中被鉴定，并发现与不同的临床特征相关。虽然MSAs对于IIM的诊断是有价值的，但是这些抗体的致病作用仍然未知。为了研究IIM的发病机制，已经建立了几种实验性肌炎的动物模型。自身免疫性肌炎、实验性自身免疫性肌炎和C蛋白诱导的肌炎的经典小鼠模型分别通过肌肉特异性抗原、肌球蛋白和骨骼C蛋白免疫建立。此外，通过用鼠重组组氨酰-tRNA合成酶Jo-1免疫产生实验性肌炎的鼠模型，其中根据获得性免疫诱导反映抗合成酶综合征的肌肉和肺部炎症。最近，发现来自免疫介导的坏死性肌病患者的人IgG（包含抗信号识别颗粒和抗3-羟基-3-甲基戊二酰辅酶A还原酶抗体）的转移在受体小鼠中诱导补体介导的肌炎。CD 8 + T细胞介导的肌炎可以依赖于针对转录中间因子1γ（TIF 1 γ）的自身免疫而建立，TIF 1 γ是由重组人TIF 1 γ免疫诱导的MSA的自身抗原。这些反映MSA相关IIMs的新小鼠模型是准确理解IIMs病理机制的有用工具。
Abstract Idiopathic inflammatory myopathies (IIMs) are characterized by inflammation of muscles and other organs. Several myositis-specific autoantibodies (MSAs) have been identified in IIMs and were found to be associated with distinct clinical features. Although MSAs are valuable for the diagnosis of IIMs, the pathogenic roles of these antibodies remain unknown. To investigate the pathogenesis of IIMs, several animal models of experimental myositis have been established. Classical murine models of autoimmune myositis, experimental autoimmune myositis, and C protein-induced myositis are established by immunization with muscle-specific antigens, myosin, and skeletal C protein, respectively. Furthermore, a murine model of experimental myositis was generated by immunization with a murine recombinant histidyl-tRNA synthetase, Jo-1, in which muscle and lung inflammation reflecting anti-synthetase syndrome are induced depending on acquired immunity. Recently, the transfer of human IgGs from patients with immune-mediated necrotizing myopathy, comprising anti-signal recognition particles and anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibodies, was found to induce complement-mediated myositis in recipient mice. CD8+ T cell-mediated myositis can be established depending on autoimmunity against transcriptional intermediary factor 1γ (TIF1γ), an autoantigen for MSAs induced by recombinant human TIF1γ immunization. These new murine models reflecting MSA-related IIMs are useful tools for accurately understanding the pathological mechanisms underlying IIMs.