摘要
Toll样受体(Toll-like receptors,TLR)作为一类能识别病原体的模式识别受体广泛存在于抗原提呈细胞中,对介导固有免疫应答和适应性免疫应答起到了重要作用.人类一共有10种TLR,可分为分布于胞膜表面的受体以及分布于胞内区室的受体两类.其中TLR7和TLR9广泛分布于人B细胞胞内,对B细胞的功能起到重要作用.TLR可通过TLR-MyD88信号通路和非MyD88途径传导信号,作用于B淋巴细胞,促进其增殖、分化、抗体分泌等.TLR7、TLR9可通过其激动剂,如含有CpG的脱氧寡核苷酸(CpG-containing oligodeoxynucleotides,CpG-ODN),刺激记忆性B细胞和幼稚B细胞增殖,继而促进浆细胞的转化,降低其凋亡,促进B细胞分泌IL-6和IL-10.不仅如此,TLR7、TLR9还可刺激B细胞分泌免疫球蛋白IgG、IgM,使抗体向IgG2a转换,阻断了IgGl和IgE的产生.近期研究证实,TLR-MyD88信号通路与STAT3信号通路有关.而STAT3基因缺陷可导致常染色体显性遗传的高IgE综合征(hyper-IgE syndrome,HIES)的发病.HIES是一类以IgE水平异常增高、湿疹、反复皮肤感染、肺炎合并多系统症状为特点的原发性免疫缺陷病.TLR-MyD88-STAT3信号通路的异常可能与STAT3缺陷的HIES的发病机制密切相关.为此,该文对TLR对B细胞的激活作用以及与STAT3和HIES的关系作一综述.
Toll-like receptors(TLR) are widely exist in antigen presenting cells as a kind of pattem recognition receptor involved in the recognition of molecular structures specific for microbial pathogens,and have an important effect on innate and adaptive immune responses.There are 10 types of TLR in human beings which can be grouped into two main categories:cell surface receptors and receptors localized in the endosome.Among all the TLRs,TLR7 and TLR9,which expressed widely in human B cells,are important to B cells' functions.Two signal transduction pathways of TLR including MyD88 pathway and non-MyD88 pathway associate with B cells activation,proliferation,differentiation and antibody secretion.TLR7 and TLR9's stimulus,such as CpG-containing oligodeoxynucleotides(ODN) can activate memory B cells and naive B cells,promote cells proliferation,plasma cells generation,cytokine secretion and protect them from apoptosis.More than that,TLR7 and TLR9 can stimulate the production of IgG and IgM,make antibody shift to IgG2a and block the production of IgG1 and IgE.Interestingly,TLR-MyD88 pathway is recently confirmed to have connection with STAT3 signal pathway.However,the mutation of STAT3 will cause autosomal dominant hyper-IgE syndrome (HIES),a primary immunodeficiency characterized by elevated IgE levels,eczema,recurrent infections,pneumonia as well as multi-system symptoms.Therefore,the pathogenesis of HIES maybe related to the inhibition of TLR-MyD88-STAT3 signal pathway.As a result,we write a review about TLR in B cell activation and STAT3 signal pathway,and discuss their connection between HIES.
出处
《国际儿科学杂志》
2018年第5期384-388,共5页
International Journal of Pediatrics
基金
National Natural Science Foundation of China(81571605)国家自然科学基金(81571605)
