Administration of activated lymphocyte-derived DNA accelerates and aggravates lupus nephritis in B6/lpr mice: a new approach to modify a lupus murine model
Administration of activated lymphocyte-derived DNA accelerates and aggravates lupus nephritis in B6/lpr mice: a new approach to modify a lupus murine model
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给予活化的淋巴细胞来源的 DNA 会加速并加重 B6/lpr 小鼠的狼疮肾炎：一种修改狼疮小鼠模型的新方法
DOI：
10.1111/cei.13147
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发表时间：
2018
影响因子：
4.6
通讯作者：
S Xiong
中科院分区：
文献类型：
--
作者：
Y Zhu;Y Yue;S Xiong
B6/lpr 小鼠品系是众所周知的系统性红斑狼疮小鼠模型，其特征是不受控制的淋巴细胞增殖和自身抗体产生。然而，其表现出狼疮性肾炎（LN）的迟发性和轻度发展，不利于该病发病机制和治疗策略的研究。我们之前的研究表明，活化的淋巴细胞源性 DNA (ALD-DNA) 可诱导 BALB/c 小鼠出现高尿蛋白水平和严重的肾小球肾炎 (GN)。在本研究中，我们尝试通过 ALD-DNA 免疫来治疗 B6/lpr 小鼠的尿蛋白产生延迟和轻度 GN。我们发现，与未活化淋巴细胞源 (UnALD)-DNA 和磷酸盐缓冲盐水 (PBS) 处理的对照组相比，ALD-DNA 免疫 4 周后，B6/lpr 小鼠的尿蛋白水平显着升高。此外，在 ALD-DNA 免疫的 B6/lpr 小鼠中观察到更严重的 GN 和肾小球免疫复合物。我们进一步探讨其机制，发现ALD-DNA免疫显着促进17型辅助性T细胞（Th17）富集，从而提高分泌自身抗体的浆细胞比例，促进抗dsDNA自身抗体的产生，导致LN加速和加重。我们的数据表明，ALD-DNA 免疫可以治疗 B6/lpr 小鼠尿蛋白产生延迟和轻度 GN，这使其更适合研究 LN 的发病机制和治疗策略。
B6/lpr mouse strain is a well-known systemic lupus erythematosus murine model characterized by uncontrolled lymphoproliferation and autoantibody production. However, it displays a delayed and mild development of lupus nephritis (LN), which is not conducive to the research of the pathogenesis and therapeutic strategies of this condition. Our previous study demonstrated that activated lymphocyte-derived DNA (ALD-DNA) could induce high urine protein levels and severe glomerulonephritis (GN) in BALB/c mice. In the present study, we tried to remedy delayed urine protein production and mild GN in B6/lpr mice via ALD-DNA immunization. We found that urine protein levels were enhanced significantly in B6/lpr mice 4 weeks after ALD-DNA immunization compared with those in unactivated lymphocyte-derived (UnALD)-DNA- and phosphate-buffered saline (PBS)-treated controls. Moreover, more serious GN and glomerular immune complex were observed in ALD-DNA-immunized B6/lpr mice. We further explored the mechanism, and found that ALD-DNA immunization promoted T helper type 17 (Th17) cell enrichment remarkably, which enhanced the proportion of autoantibody-secreting plasma cells and promoted the production of anti-dsDNA autoantibodies, leading to accelerated and aggravated LN. Our data demonstrated that ALD-DNA immunization could remedy delayed urine protein production and mild GN in B6/lpr mouse, which makes it more suitable for studies on the pathogenesis of and therapeutic strategies against LN.