K/BxN Serum-Transfer Arthritis as a Model for Human Inflammatory Arthritis.
K/BxN Serum-Transfer Arthritis as a Model for Human Inflammatory Arthritis.
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DOI：
10.3389/fimmu.2016.00213
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发表时间：
2016
影响因子：
7.3
通讯作者：
Hamilton JA
中科院分区：
文献类型：
--
作者：
Christensen AD;Haase C;Cook AD;Hamilton JA
K/BxN血清转移关节炎（STA）模型是一种小鼠模型，其中可以研究类风湿性关节炎（RA）和其他关节炎中发生的免疫机制。为了诱导K/BxN STA，将来自关节炎转基因K/BxN小鼠的血清转移到未处理小鼠中，几天后出现关节炎的表现。模型中的炎症反应由针对普遍表达的自身抗原葡萄糖-6-磷酸异构酶（G6 PI）的自身抗体驱动，导致免疫复合物的形成，所述免疫复合物驱动不同的先天免疫细胞（例如嗜中性粒细胞、巨噬细胞和可能的肥大细胞）的活化。发病机制还涉及一系列免疫介质，包括细胞因子、趋化因子、补体因子、Toll样受体、Fc受体和整联蛋白，以及参与疼痛和骨侵蚀的因子。因此，即使K/BxN STA模型仅模拟RA的效应相，它仍然涉及广泛的相关疾病介质。此外，作为关节炎的小鼠模型，K/BxN STA模型具有一些明显的优势。首先，它有一个快速和强大的关节炎发病率100%的遗传相同的动物。其次，它可以在广泛的菌株背景中诱导，因此也可以在基因缺陷菌株中诱导，以研究疾病介质的特定重要性。即使G6 PI可能不是一种必需的自身抗原，例如，在RA中，K/BxN STA模型是了解自身抗体如何通过与先天免疫系统的下游组分相互作用来驱动关节炎进展的有用工具。最后，该模型也被证明是有用的模型，其中关节炎疼痛可以进行研究。综上所述，这些特征使得K/BxN STA模型成为RA的相关模型，并且它是一种潜在的有价值的工具，特别是对于RA和其他形式的炎性关节炎的新治疗靶点的临床前筛选。在这里，我们描述的分子和细胞途径的发展K/BxN STA集中在最近的进展，了解的重要机制。此外，本文还对K/BxN STA模型与其他关节炎模型进行了比较。
The K/BxN serum-transfer arthritis (STA) model is a murine model in which the immunological mechanisms occurring in rheumatoid arthritis (RA) and other arthritides can be studied. To induce K/BxN STA, serum from arthritic transgenic K/BxN mice is transferred to naive mice and manifestations of arthritis occur a few days later. The inflammatory response in the model is driven by autoantibodies against the ubiquitously expressed self-antigen, glucose-6-phosphate isomerase (G6PI), leading to the formation of immune complexes that drive the activation of different innate immune cells such as neutrophils, macrophages, and possibly mast cells. The pathogenesis further involves a range of immune mediators including cytokines, chemokines, complement factors, Toll-like receptors, Fc receptors, and integrins, as well as factors involved in pain and bone erosion. Hence, even though the K/BxN STA model mimics only the effector phase of RA, it still involves a wide range of relevant disease mediators. Additionally, as a murine model for arthritis, the K/BxN STA model has some obvious advantages. First, it has a rapid and robust onset of arthritis with 100% incidence in genetically identical animals. Second, it can be induced in a wide range of strain backgrounds and can therefore also be induced in gene-deficient strains to study the specific importance of disease mediators. Even though G6PI might not be an essential autoantigen, for example, in RA, the K/BxN STA model is a useful tool to understand how autoantibodies, in general, drive the progression of arthritis by interacting with downstream components of the innate immune system. Finally, the model has also proven useful as a model wherein arthritic pain can be studied. Taken together, these features make the K/BxN STA model a relevant one for RA, and it is a potentially valuable tool, especially for the preclinical screening of new therapeutic targets for RA and perhaps other forms of inflammatory arthritis. Here, we describe the molecular and cellular pathways in the development of K/BxN STA focusing on the recent advances in the understanding of the important mechanisms. Additionally, this review provides a comparison of the K/BxN STA model to some other arthritis models.