肝脏 ›› 2023, Vol. 28 ›› Issue (10): 1212-1214.

• 病毒性肝炎 • 上一篇    下一篇

通过CD20单抗打破小鼠HBV免疫耐受研究Bregs细胞在慢性乙型肝炎中的作用

刘中天, 张嘉静, 林涛发, 舒丹, 王少扬   

  1. 350025 福州 厦门大学附属东方医院(中国人民解放军联勤保障部队九OO医院)感染科
  • 收稿日期:2023-06-25 出版日期:2023-10-31 发布日期:2023-12-06
  • 通讯作者: 王少扬,Email:wsyang2005@163.com
  • 基金资助:
    福建省自然科学基金面上项目(2019J01527)

Disruption of HBV immune tolerance in mice using CD20 monoclonal antibody: investigating the role of regulatory B cells in hepatitis B

LIU Zhong-tian, ZHANG Jia-jing, LIN Tao-fa, SHU Dan, WANG Shao-yang   

  1. Department of Infection, Xiamen University Affiliated Eastern Hospital (900 Hospital of the People′s Liberation Army Joint Services and Security Forces), Fuzhou 350025, China
  • Received:2023-06-25 Online:2023-10-31 Published:2023-12-06
  • Contact: WANG Shao-yang,Email:wsyang2005@163.com

摘要: 目的 通过利妥昔单抗破坏小鼠HBV感染的免疫耐受状态,了解Bregs细胞在慢性乙型肝炎发病机制中的作用。方法 用流式细胞仪动态观察慢性HBV感染小鼠模型中Bregs细胞的数量,同时测量血清IL-10水平、肝功能和凝血功能,并分析Bregs、IL-10和肝功能之间的相关性。结果 利妥昔单抗破坏的小鼠肝脏、脾脏和外周血中Bregs细胞低于没有利妥昔单抗破坏的小鼠分别为0.54(0.49,0.71)% 比 1.34(1.15,1.54)%、3.19(2.90,3.57)% 比 4.75(3.92,5.32)%、2.50(2.29,2.64)% 比 3.35(3.07,3.58)%(P<0.05);与对照组相比,利妥昔单抗破坏的小鼠血清IL-10水平也较低为21.51(14.70,28.28)pg/mL 比 32.87(27.76,35.82)pg/mL(P<0.05)。此外,实验组中Bregs细胞的变化与IL-10呈正相关(r=0.73、0.74、0.71,P<0.05)。实验组的ALT和AST水平高于对照组;实验组的IL-10水平与ALT和AST水平之间存在负相关关系。结论 Bregs细胞在慢性乙型肝炎的发病机制中通过分泌IL-10抑制炎症活动。

关键词: 调节性B细胞, 白细胞介素10, 慢性乙型肝炎

Abstract: Objective To study the role of Regulatory B cells(Bregs) in the Pathogenesis of chronic hepatitis B by Rituximab destroying the immunological tolerance state of HBV infection in mice. Methods In a mouse model of chronic HBV infection, the dynamics of Bregs populations were monitored using Flow cytometry. Additionally, serum IL-10 levels, liver function, and coagulation parameters were assessed. The correlation between Bregs, IL-10, and liver function was further analyzed. Results In mice treated with Rituximab, the percentage of Bregs was significantly reduced in the liver, spleen and peripheral blood compared to untreated mice [0.54(0.49,0.71)% vs 1.34(1.15,1.54)%;3.19(2.90,3.57)% vs 4.75(3.92,5.32)%;2.50(2.29,2.64)% vs 3.35(3.07,3.58)%; all P<0.05]. Serum IL-10 levels in Rituximab-treated mice were also significantly decreased[21.51(14.70,28.28)pg/ml vs 32.87(27.76,35.82)pg/mL,P<0.05]. Furthermore, there was a positive correlation between changes in precentages of Bregs and IL-10 levels in the experimental group(r=0.73,P<0.05;r=0.74,P<0.05;r=0.71,P<0.05). In the experimental group, elevated ALT and AST levels wereobserved compared to the control group, and these increases were inversely correlated with IL-10 levels. Conclusion Bregs play an important role in the pathogenesis of chronic hepatitis B and suppress inflammatory activity by secreting IL-10.

Key words: Regulatory B cells, Interleukin-10, Chronic hepatitis B