Inhibition of Bcl-6 Expression Ameliorates Asthmatic Characteristics in Mice  

作　　者：Chang-zhi ZHOU Xiong XIONG Wei-jun TAN Ya-fei WANG Zhen YANG Xue-ying LI Xiu-wen YANG Xiao-fan LIU Sun-feng YU Liang-chao WANG Shuang GENG 

机构地区：[1]Department of Respiratory and Critical Care Medicine,The Central Hospital of Wuhan,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430014,China [2]Department of General Surgery,Wuhan Wuchang Hospital,Wuhan University of Science and Technology,Wuhan 430063,China

出　　处：《Current Medical Science》2024年第1期110-120,共11页当代医学科学（英文）

基　　金：supported by the National Natural Science Foundation of China(No.81400020);a Scientific Research Project of the Wuhan Municipal Health and Family Planning Commission(No.WX19C30).

摘　　要：Objective The function of Bcl-6 in T follicular helper(Tfh)cell maturation is indispensable,and Tfh cells play a pivotal role in asthma.This study investigated the impact of Bcl-6 on asthmatic traits.Methods The microscopic pathological alterations,airway resistance(AR),and lung compliance(LC)were determined in asthmatic mice and Bcl-6 interference mice.The surface molecular markers of Tfh cells and the Bcl-6 mRNA and protein expression were determined by flow cytometry,RT-qPCR,and Western blotting,respectively.The relationships between the Tfh cell ratio and the IgE and IgG1 concentrations in peripheral blood mononuclear cells(PBMCs)and bronchoalveolar lavage fluid(BALF)were determined.Results Asthmatic inflammatory changes were observed in the lung tissue and were attenuated by Bcl-6 siRNA and dexamethasone(DXM).Asthmatic mice exhibited an increased AR and a decreased LC,while Bcl-6 siRNA or DXM mitigated these changes.The percentages of Tfh cells and eosinophils were significantly increased in the asthmatic mice,and they significantly decreased after Bcl-6 inhibition or DXM treatment.RT-qPCR and Western blotting analyses revealed that the Bcl-6 expression level in PBMCs was significantly higher in asthmatic mice,and it decreased following Bcl-6 inhibition or DXM treatment.The IgE expression in the serum and BALF and the B cell expression in PBMCs exhibited a similar trend.In asthmatic mice,the ratio of Tfh cells in the peripheral blood showed a strong positive correlation with the IgE levels in the serum and BALF,but not with the IgG1 levels.Conclusion The amelioration of airway inflammation and airway hyper-responsiveness is achieved through Bcl-6 suppression,which effectively hinders Tfh cell differentiation,ultimately resulting in a concurrent reduction in IgE production.

关 键 词：BCL-6 TFH ASTHMA airway hyper-responsiveness mouse model 

分 类 号：R562.25[医药卫生—呼吸系统]