Inhibition of CX3CL1 (fractalkine) improves experimental autoimmune myositis in SJL/J mice
Inhibition of CX3CL1 (fractalkine) improves experimental autoimmune myositis in SJL/J mice
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DOI：
10.4049/jimmunol.175.10.6987
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发表时间：
2005-11-15
影响因子：
4.4
通讯作者：
Miyasaka, N
中科院分区：
文献类型：
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作者：
Suzuki, F;Nanki, T;Miyasaka, N
特发性炎症性肌病是一种慢性炎症性肌肉疾病，其特征是单个核细胞在骨骼肌中的浸润。浸润性炎症细胞表达多种细胞因子和细胞毒分子。趋化因子被认为有助于炎症细胞迁移到肌肉中。用兔肌球蛋白和CFA免疫SJL/J小鼠诱导实验性自身免疫性肌炎(EAM)。在EAM小鼠病变肌肉中，CX3CL1(Fractalkine)表达于受累的单个核细胞和内皮细胞，其相应的受体CX3CR1表达于受累的CD4、CD8T细胞和巨噬细胞。经抗CX3CL1单抗治疗后，EAM小鼠的肌炎评分、坏死肌纤维数量及CD4、CD8T细胞和巨噬细胞的浸润明显减少。此外，抗CX3CL1单抗可下调肌肉中肿瘤坏死因子-α、干扰素-γ和穿孔素的mRNA表达。我们的结果提示，CX3CL1-CX3CR1相互作用在炎症细胞向EAM小鼠肌肉组织的迁移中起重要作用。这些结果也提示CX3CL1抑制和/或阻断CX3CL1-CX3CR1相互作用在特发性炎症性肌病中具有潜在的治疗作用。
Idiopathic inflammatory myopathy is a chronic inflammatory muscle disease characterized by mononuclear cell infiltration in the skeletal muscle. The infiltrated inflammatory cells express various cytokines and cytotoxic molecules. Chemokines are thought to contribute to the inflammatory cell migration into the muscle. We induced experimental autoimmune myositis (EAM) in SJL/J mice by immunization with rabbit myosin and CFA. In the affected muscles of EAM mice, CX3CL1 (fractalkine) was expressed on the infiltrated mononuclear cells and endothelial cells, and its corresponding receptor, CX3CR1, was expressed on the infiltrated CD4 and CD8 T cells and macrophages. Treatment of EAM mice with anti-CX3CL1 mAb significantly reduced the histopathological myositis score, the number of necrotic muscle fibers, and infiltration of CD4 and CD8 T cells and macrophages. Furthermore, treatment with anti-CX3CL1 mAb down-regulated the mRNA expression of TNF-alpha, IFN-gamma, and perforin in the muscles. Our results suggest that CX3CL1-CX3CR1 interaction plays an important role in inflammatory cell migration into the muscle tissue of EAM mice. The results also point to the potential therapeutic usefulness of CX3CL1 inhibition and/or blockade of CX3CL1-CX3CR1 interaction in idiopathic inflammatory myopathy.