Journal of Peking University(Health Sciences) ›› 2019, Vol. 51 ›› Issue (3): 445-450. doi: 10.19723/j.issn.1671-167X.2019.03.011

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Role of erythroblast-like Ter cells in the pathogenesis of collagen-induced arthritis

Ping WANG1,Jing SONG1,Xiang-yu FANG1,Xin LI1,Xu LIU1,Yuan JIA1,Zhan-guo LI1,2,Fan-lei HU1△()   

  1. 1. Department of Rheumatology and Immunology, Peking University People’s Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis, Beijing 100044, China;
    2. State Key Laboratory of Natural and Biomime-tic Drugs, Peking University School of Pharmaceutical Sciences, Beijing 100191, China
  • Received:2019-03-18 Online:2019-06-18 Published:2019-06-26
  • Supported by:
    Supported by the National Natural Science Foundation of China (81671604, 81302554, 31530020,81801617), the Beijing Nova Program (Z181100006218044) and the Fundamental Research Funds for the Central Universities: Peking University Clinical Medicine Plus X-Young Scholars Project (PKU2019LCXQ018)

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.

Key words: Arthritis, experimental, Ter cells, Inflammation, Collagen

CLC Number: 

  • R593.22

Figure 1

Distribution of Ter cells in the spleen of different strains of mice A,gating strategies for Ter cells in the spleen of mice; B, the frequencies of Ter cells in C57BL/6, Balb/c and DBA/1 mice."

Figure 2

Ter cells were significantly increased in CIA mice (n=6) CIA, collagen-induced arthritis. Frequencys of Ter cells in the spleen of na?ve and CIA mice. Ter cells were increased markbly in CIA mice compared with na?ve mice."

Figure 3

Correlation analysis of Ter cell frequencies with joint score, T and B cell subsets A, The differences of the frequencies of Ter, Th1, Th17 and GC-B cells between the mice with high score and low score at the peak stage of CIA; B, Correlation analysis of Ter cell frequencies with T and B cell subsets."

Figure 4

Dynamic changes of Ter cells in different stages of CIA (n=6) Frequencys of Ter cells in the spleen of na?ve and CIA mice at different stages. Ter cells were decreased markbly in CIA mice at late stage compared with peak stage."

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