炎症性关节炎的KRN小鼠模型。

The KRN mouse model of inflammatory arthritis.

作者信息

Kyburz Diego, Corr Maripat

机构信息

Department of Rheumatology, University Hospital of Zurich, Gloriastrasse 25, 8091, Zurich, Switzerland.

出版信息

Springer Semin Immunopathol. 2003 Aug;25(1):79-90. doi: 10.1007/s00281-003-0131-5.

Abstract

In 1996 a new murine model of spontaneous arthritis was described by the group of Benoist and Mathis. Mice transgenic for a T cell receptor recognizing an epitope of bovine RNase and bred onto a NOD background developed severe destructive arthritis, which resembles human rheumatoid arthritis in many respects. The development of disease requires the presence of T and B lymphocytes and is dependent on the MHC class II molecule I-A(g7). B cell activation by antigen and an additional CD40-CD40 ligand interaction was found to give rise to the production of autoantibodies. Glucose-6-phosphate isomerase was identified as the target of the autoantibodies; moreover, the transgenic T cells were demonstrated to exhibit a dual specificity for both bovine RNase and glucose-6-phosphate isomerase. Importantly, the arthritis is serum transferable to normal recipients, enabling the examination of the pathogenic mechanisms of joint inflammation and destruction. Recent studies suggest the crucial involvement of the innate immune system in the development of antibody-induced arthritis. Complement components, Fc receptors and neutrophils are indispensable for disease induction. An overview of the existing data is given and the emerging concepts of the pathogenesis of the K/BxN arthritis are discussed with respect to their relevance for human rheumatoid arthritis. Because of the reliable and robust induction of joint inflammation by serum transfer this new disease model has been and will be a valuable means to address the as-yet-unanswered key questions related to the development of arthritis.

摘要

1996年,贝努瓦(Benoist)和马蒂斯(Mathis)团队描述了一种新的自发性关节炎小鼠模型。转染了识别牛核糖核酸酶表位的T细胞受体并培育至非肥胖型糖尿病(NOD)背景的小鼠会发展出严重的破坏性关节炎,这种关节炎在许多方面类似于人类类风湿性关节炎。疾病的发展需要T淋巴细胞和B淋巴细胞的存在,并且依赖于MHC II类分子I-A(g7)。发现抗原激活B细胞以及额外的CD40 - CD40配体相互作用会引发自身抗体的产生。葡萄糖-6-磷酸异构酶被确定为自身抗体的靶标;此外,转基因T细胞被证明对牛核糖核酸酶和葡萄糖-6-磷酸异构酶都具有双重特异性。重要的是,这种关节炎的血清可转移至正常受体,从而能够研究关节炎症和破坏的致病机制。最近的研究表明先天免疫系统在抗体诱导的关节炎发展中起关键作用。补体成分、Fc受体和中性粒细胞对于疾病诱导是不可或缺的。本文给出了现有数据的概述,并讨论了K/BxN关节炎发病机制的新观点及其与人类类风湿性关节炎的相关性。由于通过血清转移能可靠且有力地诱导关节炎症,这种新的疾病模型一直并将继续是解决与关节炎发展相关的尚未解答的关键问题的宝贵手段。

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