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

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

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。

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.