下调和上调
TLR9型
转染
B细胞
基因沉默
αBκ
分子生物学
幼稚B细胞
发病机制
医学
记忆B细胞
癌症研究
免疫学
生物
抗体
NF-κB
炎症
T细胞
细胞培养
免疫系统
DNA甲基化
基因表达
抗原提呈细胞
基因
生物化学
遗传学
作者
Jinlei Sun,Hao-Ze Zhang,Suying Liu,Chaofeng Lian,Zhilei Chen,Tihong Shao,Shuo Zhang,Liling Zhao,Chengmei He,Mu Wang,Wen Zhang,Hua Chen,Fengchun Zhang
标识
DOI:10.1136/annrheumdis-2019-216428
摘要
Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterised by aberrant B cell hyperactivation, whose mechanism is partially understood.We performed whole transcriptome sequencing of B cells from three pSS patients and three matched healthy controls (HC). Differentially expression genes (DEGs) were confirmed with B cells from 40 pSS patients and 40 HC by quantitative PCR and western blot. We measured the proliferation potential and immunoglobulins production of siRNA-transfected or plasmid-transfected B cells stimulated with cytosine-phosphate-guanine (CpG) or anti-IgM. We also explored Toll-like receptor 9 (TLR9) signalling to reveal the potential mechanism of B cell hyperactivation in pSS.We identified 77 upregulated and 32 downregulated DEGs in pSS B cells. We confirmed that epithelial stromal interaction (EPST1) expression in pSS B cells was significantly higher than that from HCs. EPSTI1-silencing B cells stimulated with CpG were less proliferated and produced lower level of IgG and IgM comparing with control B cells. EPSTI1-silencing B cells expressed lower level of p-p65 and higher level of IκBα, and B cells with overexpressed EPSTI1 showed higher level of p-p65 and lower level of IκBα. Finally, IκBα degradation inhibitor Dehydrocostus Lactone treatment attenuated p65 phosphorylation promoted by EPSTI1.Elevated EPSTI1 expression in pSS B cells promoted TLR9 signalling activation and contributed to the abnormal B cell activation, which was promoted by facilitating p65 phosphorylation and activation of NF-κB signalling via promoting IκBα degradation. EPSTI1 might be implicated in pSS pathogenesis and was a potential therapeutic target of pSS.
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