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 micro...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.展开更多
自滤泡辅助性T细胞(follicular helper T cells,Tfh细胞)发现以来,大量证据表明与炎症性肠病的发病有关.Tfh细胞及其亚群分泌不同细胞因子皆可在炎症性肠病的发病过程中扮演重要角色,为靶向治疗炎症性肠病提供重要思路.BCL-6信号作为Tf...自滤泡辅助性T细胞(follicular helper T cells,Tfh细胞)发现以来,大量证据表明与炎症性肠病的发病有关.Tfh细胞及其亚群分泌不同细胞因子皆可在炎症性肠病的发病过程中扮演重要角色,为靶向治疗炎症性肠病提供重要思路.BCL-6信号作为Tfh细胞分化途径上的关键性转录因子,可调控Tfh细胞的增殖、分化.在BCL-6信号缺乏时无法产生Tfh细胞,且BCL-6信号也可通过正性调控、负性调控以及表观遗传学等多种途径有效调控Tfh细胞的分化.在BCL-6信号调控异常时可导致Tfh的分化异常导致炎症性肠病的发生.因此可以通过干预BCL-6信号来调控Tfh细胞分化来作为治疗炎症性肠病新的有效靶点.展开更多
目的:探讨新疆维吾尔族、汉族弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)患者Bcl-6、c-myc基因易位的差异及其临床意义。方法:采用荧光免疫原位杂交(FISH)方法,对233例DLBCL活体石蜡切片进行Bcl-6、c-myc基因检测。观察Bc...目的:探讨新疆维吾尔族、汉族弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)患者Bcl-6、c-myc基因易位的差异及其临床意义。方法:采用荧光免疫原位杂交(FISH)方法,对233例DLBCL活体石蜡切片进行Bcl-6、c-myc基因检测。观察Bcl-6、c-myc基因易位与DLBCL患者临床资料的关系,并对不同民族在不同亚型DLBCL中Bcl-6、c-myc基因易位的情况进行比较。结果:233例DLBCL中,Bcl-6基因重排51例,占21.89%;c-myc基因重排39例,占16.74%;Bcl-6基因易位的表达与患者年龄、性别、发病部位、临床分期和LDH水平无显著相关(P>0.05),而与民族、IPI评分、结外侵犯、B症状、DLBCL不同亚型和近期疗效有相关性(P<0.05);c-myc基因易位的表达与患者年龄、性别、发病部位、临床分期、LDH水平和DLBCL不同亚型无明显相关性(P>0.05),而与民族、IPI评分、结外侵犯、B症状和近期疗效有相关性(P<0.05);维、汉不同民族GCB中Bcl-6、c-myc基因易位比较差异均无统计学意义(P>0.05);维、汉不同民族非生发中心活化B细胞(non-GCB)中Bcl-6、c-myc基因易位比较差异有统计学意义(P<0.05)。结论:Bcl-6,C-myc基因易位的表达与维、汉不同民族、IPI评分、结外侵犯、B症状和近期疗效有相关性;维、汉民族non-GCB亚组中Bcl-6、c-myc基因易位存在差异。展开更多
目的探讨bcl-2、bcl-6、CD10、MUM1在弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中的表达及与亚分类的关系。方法应用免疫组织化学S-P法,检测60例弥漫性大B细胞淋巴瘤标本中bcl-2、bcl-6、CD10、MUM1蛋白的表达水平。结...目的探讨bcl-2、bcl-6、CD10、MUM1在弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中的表达及与亚分类的关系。方法应用免疫组织化学S-P法,检测60例弥漫性大B细胞淋巴瘤标本中bcl-2、bcl-6、CD10、MUM1蛋白的表达水平。结果bcl-2、bcl-6、CD10、MUM1在60例弥漫性大B细胞淋巴瘤中的表达率分别为55.0%(33/60)、48.3%(29/60)、46.7%(28/60)、58.3%(35/60),其中GCB占55.0%(33/60),non-GCB占45.0%(27/60)。GCB、non-GCB中bcl-2的表达差异具有显著性。在non-GCB中,bcl-6+与bcl-6-的病例bcl-2表达的差异具有显著性。结论该组病例GCB所占的比率超过non-GCB,bcl-2在DLBCL亚分类中可能具有一定的作用。展开更多
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).
文摘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.
文摘自滤泡辅助性T细胞(follicular helper T cells,Tfh细胞)发现以来,大量证据表明与炎症性肠病的发病有关.Tfh细胞及其亚群分泌不同细胞因子皆可在炎症性肠病的发病过程中扮演重要角色,为靶向治疗炎症性肠病提供重要思路.BCL-6信号作为Tfh细胞分化途径上的关键性转录因子,可调控Tfh细胞的增殖、分化.在BCL-6信号缺乏时无法产生Tfh细胞,且BCL-6信号也可通过正性调控、负性调控以及表观遗传学等多种途径有效调控Tfh细胞的分化.在BCL-6信号调控异常时可导致Tfh的分化异常导致炎症性肠病的发生.因此可以通过干预BCL-6信号来调控Tfh细胞分化来作为治疗炎症性肠病新的有效靶点.
文摘目的:探讨新疆维吾尔族、汉族弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)患者Bcl-6、c-myc基因易位的差异及其临床意义。方法:采用荧光免疫原位杂交(FISH)方法,对233例DLBCL活体石蜡切片进行Bcl-6、c-myc基因检测。观察Bcl-6、c-myc基因易位与DLBCL患者临床资料的关系,并对不同民族在不同亚型DLBCL中Bcl-6、c-myc基因易位的情况进行比较。结果:233例DLBCL中,Bcl-6基因重排51例,占21.89%;c-myc基因重排39例,占16.74%;Bcl-6基因易位的表达与患者年龄、性别、发病部位、临床分期和LDH水平无显著相关(P>0.05),而与民族、IPI评分、结外侵犯、B症状、DLBCL不同亚型和近期疗效有相关性(P<0.05);c-myc基因易位的表达与患者年龄、性别、发病部位、临床分期、LDH水平和DLBCL不同亚型无明显相关性(P>0.05),而与民族、IPI评分、结外侵犯、B症状和近期疗效有相关性(P<0.05);维、汉不同民族GCB中Bcl-6、c-myc基因易位比较差异均无统计学意义(P>0.05);维、汉不同民族非生发中心活化B细胞(non-GCB)中Bcl-6、c-myc基因易位比较差异有统计学意义(P<0.05)。结论:Bcl-6,C-myc基因易位的表达与维、汉不同民族、IPI评分、结外侵犯、B症状和近期疗效有相关性;维、汉民族non-GCB亚组中Bcl-6、c-myc基因易位存在差异。
文摘目的探讨bcl-2、bcl-6、CD10、MUM1在弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中的表达及与亚分类的关系。方法应用免疫组织化学S-P法,检测60例弥漫性大B细胞淋巴瘤标本中bcl-2、bcl-6、CD10、MUM1蛋白的表达水平。结果bcl-2、bcl-6、CD10、MUM1在60例弥漫性大B细胞淋巴瘤中的表达率分别为55.0%(33/60)、48.3%(29/60)、46.7%(28/60)、58.3%(35/60),其中GCB占55.0%(33/60),non-GCB占45.0%(27/60)。GCB、non-GCB中bcl-2的表达差异具有显著性。在non-GCB中,bcl-6+与bcl-6-的病例bcl-2表达的差异具有显著性。结论该组病例GCB所占的比率超过non-GCB,bcl-2在DLBCL亚分类中可能具有一定的作用。
