| 成红细胞样Ter细胞在胶原诱导性关节炎发病中的作用 |
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| 引用本文： | 王平,宋婧,方翔宇,李鑫,刘栩,贾园,粟占国,胡凡磊. 成红细胞样Ter细胞在胶原诱导性关节炎发病中的作用[J]. 北京大学学报(医学版), 2019, 51(3): 445-450. DOI: 10.19723/j.issn.1671-167X.2019.03.011 |
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| 作者姓名： | 王平 宋婧 方翔宇 李鑫 刘栩 贾园 粟占国 胡凡磊 |
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| 作者单位： | 北京大学人民医院风湿免疫科,风湿病机制及免疫诊断北京市重点实验室,北京100044;北京大学人民医院风湿免疫科,风湿病机制及免疫诊断北京市重点实验室,北京100044;北京大学药学院天然药物及仿生药物国家重点实验室,北京100191 |
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| 基金项目： | 国家自然科学基金(81671604、81302554、31530020、81801617)、北京市科技新星计划(Z181100006218044)和北京大学临床医学+X青年专项(PKU2019LCXQ018)-中央高校基本科研业务费 |
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| 摘 要： | 目的 通过检测Ter细胞在不同发病阶段胶原诱导性关节炎(collagen-induced arthritis,CIA)小鼠脾脏中的数量变化及高峰期CIA小鼠脾脏Ter细胞与关节评分和T、B细胞亚群比例的相关性,探讨Ter细胞在CIA发生和发展中的作用,从而进一步深入理解类风湿关节炎的发病机制。方法 6~8周的DBA/1小鼠进行CIA模型的诱导,二次免疫后开始对CIA小鼠进行关节评分。根据发病时间和关节评分将CIA分为发病早期、高峰期、晚期三个阶段。发病高峰期小鼠根据最终关节评分再分为高评分组(>8分)和低评分组(≤8分),流式细胞术检测na?ve小鼠和各个阶段CIA小鼠脾脏中Ter细胞比例及发病高峰期CIA小鼠脾脏T、B 细胞亚群比例,并进行关联分析。结果 发病高峰期CIA小鼠脾脏Ter细胞比例较na?ve小鼠明显升高(8.522%±2.645% vs. 1.937%±0.725%,P<0.01), 高评分组小鼠脾脏Ter细胞比例明显低于低评分组(6.217%±0.841% vs. 10.827%±0.917%,P<0.01)。高评分组小鼠脾脏Th1细胞比例明显高于低评分组(1.337%±0.110% vs. 0.727%±0.223%,P<0.05),高评分组小鼠脾脏Th17细胞比例高于低评分组(0.750%±0.171% vs. 0.477%±0.051%,P=0.099),高评分组小鼠脾脏生发中心B(germinal center B,GC-B)细胞比例明显高于低评分组(1.243%±0.057% vs. 1.097%±0.015%,P<0.05)。相关性分析结果显示,发病高峰期CIA小鼠脾脏Ter细胞比例与CD4 +T、Th1、Th17、GC-B细胞比例均呈强负相关,与B10细胞比例呈强正相关,相关性均有统计学意义,提示这群细胞在CIA中可能具有保护作用。动态变化研究显示,随着疾病进展,发病晚期CIA小鼠脾脏Ter细胞比例较高峰期明显降低(0.917%±0.588% vs. 8.522%±2.645%,P<0.001), 进一步提示这群细胞在关节炎中的保护作用。 结论 Ter细胞在发病高峰期CIA小鼠脾脏中明显增加,与小鼠关节评分及致病性免疫细胞比例呈负相关,与保护性免疫细胞比例呈正相关,发病晚期CIA小鼠Ter细胞比例明显降低,提示Ter细胞可能作为一种保护性细胞参与类风湿关节炎的发生和发展,但其具体作用及机制仍需后续进一步的体内及体外实验验证。
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| 关 键 词： | 关节炎 实验性 Ter细胞 炎症 胶原 |
| 收稿时间： | 2019-03-18 |
Role of erythroblast-like Ter cells in the pathogenesis of collagen-induced arthritis |
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| Ping WANG,Jing SONG,Xiang-yu FANG,Xin LI,Xu LIU,Yuan JIA,Zhan-guo LI,Fan-lei HU. Role of erythroblast-like Ter cells in the pathogenesis of collagen-induced arthritis[J]. Journal of Peking University. Health sciences, 2019, 51(3): 445-450. DOI: 10.19723/j.issn.1671-167X.2019.03.011 |
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| Authors: | Ping WANG Jing SONG Xiang-yu FANG Xin LI Xu LIU Yuan JIA Zhan-guo LI Fan-lei HU |
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| Affiliation: | Department of Rheumatology and Immunology, Peking University People’s Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis, Beijing 100044, China;
State Key Laboratory of Natural and Biomime-tic Drugs, Peking University School of Pharmaceutical Sciences, Beijing 100191, China |
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| Abstract: | Objective: To explore the role of Ter cells in the development of the collagen-induced arthritis (CIA), we detected their quantity changes in the spleen of different stages of CIA mice and analyzed the correlation between Ter cells and the joint scores, and we also analyzed the correlation between Ter cells and the frequencies of T and B cell subsets, so as to further understand the pathogenesis of rheumatoid arthritis.Methods: The six to eight weeks DBA/1 mice were used to prepare CIA model. After the second immunization, we began to evaluate the joint score. According to the time of CIA onset and the joint score, the CIA mice were divided into three stages: early, peak and late stages. According to the final joint score, the CIA mice at the peak stage were subdivided into the high score group (score>8) and the low score group (score≤8). The frequencies of Ter cells in the spleen of the na?ve mice and the CIA mice at various stages and the frequencies of T and B cell subsets in the spleen of the CIA mice at the peak stage were detected by flow cytometry, then we carried on the correlation analysis. Results: The frequencies of Ter cells in the spleen of the CIA mice was significantly higher than those of the na?ve mice (8.522%±2.645% vs. 1.937%±0.725%, P<0.01), the frequencies of Ter cells in the spleen of the high score group mice was significantly lower than those of the low score group (6.217%±0.841% vs. 10.827%±0.917%, P<0.01). The frequencies of Th1 cells in the spleen of the high score group mice was significantly higher than those of the low score group mice (1.337%±0.110% vs. 0.727%±0.223%, P<0.05). The frequencies of Th17 cells in the spleen of the high score group mice was higher than those of the low score group mice (0.750%±0.171% vs. 0.477%±0.051%, P=0.099). The frequencies of germinal center B cells in the spleen of the high score group mice was significantly higher than those of the low score group mice (1.243%±0.057% vs. 1.097%±0.015%, P<0.05). Correlation analysis results showed that the frequencies of Ter cells in the spleen of the CIA mice at the peak stage was strongly negatively correlated with the frequencies of CD4 + T, Th1, Th17, and germinal center B cells, and was strongly positively correlated with the frequencies of B10 cells, indicating that these cells might have a protective effect in CIA. Studies on dynamic changes showed that the frequencies of Ter cells in the spleen of the CIA mice at the late stage was significantly lower than those at the peak stage (0.917%±0.588% vs. 8.522%±2.645%, P<0.001), suggesting the protective effect of these cells in arthritis. Conclusion: Ter cells were significantly increased in the spleen of the CIA mice at peak stage, and were negatively correlated with joint scores and pathogenic immune cells, and positively correlated with protective immune cells. Ter cells were significantly decreased in the spleen of the CIA mice at the late stage. What we mentioned above suggests that Ter cells might be involved in the progression of rheumatoid arthritis as an immunomodulatory cell,but further in vivo and in vitro experiments are needed to verify its specific effects and mechanism. |
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| Keywords: | Arthritis experimental Ter cells Inflammation Collagen |
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