Laboratory of Immunobiology, Rega Institute - University of Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Cytokine Growth Factor Rev. 2011 Oct-Dec;22(5-6):339-44. doi: 10.1016/j.cytogfr.2011.11.003. Epub 2011 Nov 25.
In this review, we discuss our studies on the pathogenesis of collagen-induced arthritis (CIA) and related mouse models for rheumatoid arthritis. Of note, these models invariably rely on the use of complete Freund's adjuvant (CFA). Our analysis has focused on explaining the dichotomous - either protective or disease-promoting - role of endogenous IFN-γ. Induction of a myelopoietic burst by CFA was identified as an important and underestimated factor in mediating the role of IFN-γ and other cytokines (IL-6, IL-17, GCP-2, RANK-L). Myelopoiesis provides an excess in precursors for joint-infiltrating neutrophils and osteoclasts. We postulate that classical CIA is primarily an auto-inflammatory disease, in part because of a strong innate immune response to the adjuvant. Superimposed on this, collagen-specific auto-immunity reinforces inflammatory reactivity in joints.
在这篇综述中，我们讨论了我们在胶原诱导性关节炎 (CIA)发病机制及相关类风湿关节炎小鼠模型方面的研究。值得注意的是，这些模型无一例外地依赖于使用完全弗氏佐剂 (CFA)。我们的分析重点解释了内源性 IFN-γ 的双重作用——保护性或促病性。CFA 诱导的髓系爆发被确定为介导 IFN-γ 和其他细胞因子（IL-6、IL-17、GCP-2、RANK-L）作用的一个重要且被低估的因素。髓系发生提供了过量的关节浸润中性粒细胞和破骨细胞前体。我们假设经典 CIA 主要是一种自身炎症性疾病，部分原因是对佐剂存在强烈的先天免疫反应。在此基础上，胶原特异性自身免疫增强了关节的炎症反应性。
