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小鼠类风湿性关节炎的过继转移模型

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice.

作者信息

Ma Zijun, Zheng Na, Wei Yingying, Zhong Jixin

机构信息

Department of Rheumatology, Fujian Institute of Clinical Immunology, Fujian Medical University Union Hospital; Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.

Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology;

出版信息

J Vis Exp. 2025 Jun 6(220). doi: 10.3791/68196.

Abstract

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disorder that may result in joint damage, deformities, disability, and even death. Due to its complex etiology and heterogeneous clinical presentation, current treatment strategies remain inadequate in effectively controlling disease progression, particularly in achieving early diagnosis and providing personalized therapies. Therefore, developing novel therapeutic approaches is crucial. To achieve this, reliable animal models are essential for investigating the pathogenesis of RA. Currently, several animal models of RA are used, including the collagen-induced arthritis model (CIA), the K/BxN model, and the SKG mouse. Although these models can successfully mimic the immune mechanisms and clinical manifestations of RA, they each have notable limitations. In this protocol, we describe the process of establishing an RA mouse model through the adoptive transfer of CD4 T cells from SKG mice. Compared to conventional models, this model offers a shorter establishment time and a higher incidence rate (100%) in C57BL/6 mice. It is relatively cost-effective, involves straightforward procedures, and reliably replicates T-cell-mediated immune responses, ensuring superior experimental control and reproducibility. We conducted a comprehensive evaluation of the model, assessing the clinical phenotype such as joint symptoms. Through clinical phenotype assessment, we observed significant joint swelling and inflammatory responses. Additionally, using PCR technology to measure the expression levels of key transcription factors, we found that this model effectively simulates T cell-mediated immune responses and key pathological features of RA. With this model, researchers can better simulate the T cell-mediated immune response and key pathological features of RA, thus providing a reliable and effective experimental tool for studying immune mechanisms and pathological progression and developing novel therapies for RA.

摘要

类风湿关节炎(RA)是一种慢性全身性自身免疫性炎症性疾病,可导致关节损伤、畸形、残疾甚至死亡。由于其病因复杂且临床表现异质性,目前的治疗策略在有效控制疾病进展方面仍然不足,尤其是在实现早期诊断和提供个性化治疗方面。因此,开发新的治疗方法至关重要。要实现这一点,可靠的动物模型对于研究RA的发病机制必不可少。目前,使用了几种RA动物模型,包括胶原诱导性关节炎模型(CIA)、K/BxN模型和SKG小鼠。尽管这些模型可以成功模拟RA的免疫机制和临床表现,但它们各自都有显著的局限性。在本方案中,我们描述了通过转输SKG小鼠的CD4 T细胞建立RA小鼠模型的过程。与传统模型相比,该模型建立时间更短,在C57BL/6小鼠中的发病率更高(100%)。它相对具有成本效益,操作简单,能可靠地复制T细胞介导的免疫反应,确保了更好的实验可控性和可重复性。我们对该模型进行了全面评估,评估了诸如关节症状等临床表型。通过临床表型评估,我们观察到明显的关节肿胀和炎症反应。此外,使用PCR技术测量关键转录因子的表达水平,我们发现该模型有效地模拟了T细胞介导的免疫反应和RA的关键病理特征。利用这个模型,研究人员可以更好地模拟RA的T细胞介导的免疫反应和关键病理特征,从而为研究免疫机制和病理进展以及开发RA的新疗法提供一个可靠而有效的实验工具。

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