Deletion of Either CD55 or CD97 Ameliorates Arthritis in Mouse Models
Deletion of Either CD55 or CD97 Ameliorates Arthritis in Mouse Models
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DOI：
10.1002/art.27347
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发表时间：
2010-04-01
影响因子：
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通讯作者：
Hamann, Jorg
中科院分区：
文献类型：
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作者：
Hoek, Robert M.;de launay, Daphne;Hamann, Jorg
客观的。 CD55（衰变加速因子）以其在补体系统负调节中的作用而闻名。事实上，缺乏这种分子会导致许多自身免疫性疾病模型的疾病恶化。然而，CD55 大量存在于成纤维样滑膜细胞上，并且也是粘附类七螺旋受体 CD97 的配体，该受体由浸润巨噬细胞表达。使用 CD97 抗体治疗可改善 DBA/1 小鼠胶原诱导的类风湿性关节炎 (RA) 模型，但 CD55 的净贡献尚不清楚。本研究旨在调查 CD55 在实验性 RA 中的作用。方法。使用胶原蛋白诱导和 K/BxN 血清转移模型在野生型、CD55(-/-) 和 CD97(-/-) 小鼠中诱导关节炎。随着时间的推移监测关节炎的发病率，并通过临床和免疫组织化学评估来评估疾病活动性。结果。与许多炎症性疾病模型中的观察结果相反，CD55 的缺乏导致 RA 实验模型中关节炎的减少。与先前报道的抗CD97抗体治疗的效果一致，与野生型对照相比，CD97(-/-)小鼠的关节炎活性降低。结论。我们的研究结果表明，两种不同的关节炎模型中缺乏 CD55 或 CD97 会增加对该疾病的抵抗力。这些发现深入了解了 CD55 与 CD97 相互作用在 RA 发病机制中的作用，并表明破坏 CD55/CD97 的治疗策略可能在临床上有益。
Objective. CD55 (decay-accelerating factor) is best known for its role in the negative regulation of the complement system. Indeed, lack of this molecule leads to disease aggravation in many autoimmune disease models. However, CD55 is abundantly present on fibroblast-like synoviocytes and is also a ligand of the adhesion-class heptahelical receptor CD97, which is expressed by infiltrating macrophages. Treatment with antibodies to CD97 ameliorates the collagen-induced model of rheumatoid arthritis (RA) in DBA/1 mice, but the net contribution of CD55 is unknown. This study was undertaken to investigate the role of CD55 in experimental RA.Methods. Arthritis was induced in wild-type, CD55(-/-), and CD97(-/-) mice using collagen-induced and K/BxN serum-transfer models. Incidence of arthritis was monitored over time, and disease activity was assessed by clinical and immunohistochemical evaluation.Results. In contrast to observations in many inflammatory disease models, lack of CD55 resulted in decreased arthritis in experimental models of RA. Consistent with the previously reported effects of anti-CD97 antibody treatment, CD97(-/-) mice had reduced arthritis activity compared with wild-type controls.Conclusion. Our findings indicate that the lack of CD55 or CD97 in 2 different models of arthritis increases resistance to the disease. These findings provide insight into a role for CD55 interaction with CD97 in the pathogenesis of RA and suggest that therapeutic strategies that disrupt CD55/CD97 may be clinically beneficial.