关贸总协定3
生物
FOXP3型
基因敲除
BCL6公司
免疫学
抗体
RNA干扰
癌症研究
重症肌无力
小发夹RNA
转录因子
B细胞
免疫系统
生发中心
核糖核酸
细胞凋亡
基因
生物化学
作者
Xin Ning,Lei Fu,Zhongjun Shao,Mingrui Guo,Xiuying Zhang,Yong Zhang,Changxin Dou,Shuangshuang Zheng,Xia Shen,Yunlong Yao,Jiao Wang,Jinhua Wang,Guiyun Cui,Yonghai Liu,Deqin Geng,Chengshan Xiao,Zunsheng Zhang,Rong Dong
标识
DOI:10.1016/j.mcn.2013.12.006
摘要
Follicular helper T (Tfh) cells are dedicated to providing help to B cells and are strongly associated with antibody-mediated autoimmune disease. B cell lymphoma 6 (Bcl-6) is a key transcription factor of Tfh cells, and IL-21 is known to be a critical cytokine produced by Tfh cells. We silenced Bcl-6 gene expression using RNA interference (RNAi) delivered by a lentiviral vector, to evaluate the therapeutic role of Bcl-6 short hairpin RNAs (shRNAs) in experimental autoimmune myasthenia gravis (EAMG). Our data demonstrate that CD4(+)CXCR5(+)PD-1(+) Tfh cells, Bcl-6 and IL-21 were significantly increased in EAMG mice, compared with controls. In addition, we found that frequencies of Tfh cells were positively correlated with the levels of serum anti-AChR Ab. In-vivo transduction of lenti-siRNA-Bcl6 ameliorates the severity of ongoing EAMG with decreased Tfh cells, Bcl-6 and IL-21 expression, and leads to decreased anti-AChR antibody levels. Furthermore, we found that siRNA knockdown of Bcl-6 expression increases the expression of Th1(IFN-γ, T-bet) and Th2 markers (IL-4 and GATA3), but failed to alter the expression of Th17-related markers (RORγt, IL-17) and Treg markers (FoxP3). Our study suggests that Tfh cells contribute to the antibody production and could be one of the most important T cell subsets responsible for development and progression of EAMG or MG. Bcl-6 provides a promising therapeutic target for immunotherapy not only for MG, but also for other antibody-mediated autoimmune diseases.
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