Inhibition of fractalkine ameliorates murine collagen-induced arthritis
Inhibition of fractalkine ameliorates murine collagen-induced arthritis
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DOI：
10.4049/jimmunol.173.11.7010
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发表时间：
2004-12-01
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：
Nanki, T;Urasaki, Y;Miyasaka, N
类风湿性关节炎（RA）是一种慢性炎症性疾病，与多个关节滑膜中大量炎症细胞浸润有关。我们和其他人已经证明fractalkine (FKN/CX3CL1)，一种表达在RA滑膜的成纤维细胞样滑膜细胞和内皮细胞上的趋化因子，可能有助于T细胞、巨噬细胞和树突状细胞的积累，这些细胞表达CX3CR1 （FKN的受体）。这种相互作用可能涉及炎症细胞与内皮细胞的粘附、滑膜的迁移和细胞因子的产生。在本研究中，我们检测了FKN抑制对小鼠胶原诱导关节炎的影响。与对照组相比，抗fkn单抗可显著降低临床关节炎评分，并减少滑膜炎症细胞浸润和骨侵蚀。然而，抗fkn单抗不影响CII刺激的脾T细胞血清抗II型胶原IgG或ifn - γ的产生。此外，用抗fkn单抗治疗可抑制过继转移的脾巨噬细胞向炎症滑膜的迁移。我们的研究结果表明，抗fkn单抗通过抑制炎症细胞向滑膜的浸润来改善关节炎。因此，FKN可能成为治疗RA的新靶点分子。
Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with massive infiltration of inflammatory cells in the synovium of multiple joints. We and others have shown that fractalkine (FKN/CX3CL1), a chemokine expressed on fibroblast-like synoviocytes and endothelial cells in RA synovium, may contribute to the accumulation of T cells, macrophages, and dendritic cells, which express CX3CR1, the receptor for FKN. This interaction might be involved in adhesion of the inflammatory cells to endothelial cells, migration into the synovium, and cytokine production. In this study, we examined the effect of FKN inhibition on murine collagen-induced arthritis. Anti-FKN mAb significantly lowered clinical arthritis score compared with control Ab, and reduced infiltration of inflammatory cells and bone erosion in the synovium. However, anti-FKN mAb did not affect the production of either serum anti-collagen type II (CII) IgG or IFN-gamma by CII-stimulated splenic T cells. Furthermore, treatment with anti-FKN mAb inhibited migration of adoptively transferred splenic macrophages into the inflamed synovium. Our results suggest that anti-FKN mAb ameliorates arthritis by inhibiting infiltration of inflammatory cells into the synovium. Thus, FKN can be a new target molecule for the treatment of RA.