Toll样受体信号通路的负调控

综述了Toll样受体(Toll-like receptors,TLRs)介导炎症反应信号通路的负调控机理．TLRs可以被病原体激活并迅速启动炎症反应,对先天性和获得性免疫反应起着重要调节作用．TLRs介导的免疫反应必须受到严格的调控,持续激活状态可长时间高表达炎症因子,导致机体产生慢性炎症、自身免疫紊乱和其他TLRs相关疾病．正常生理状态下,机体存在着多种TLRs的负调控机制,以维持免疫反应的平衡．该领域的研究近年来取得了重要进展,为许多免疫相关疾病的治疗提供了线索．     

microRNA参与脓毒症免疫调控机制研究进展

脓毒症是重症监护病房(ICU)患者死亡的重要原因之一,因其高患病率、高死亡率、高治疗费用的特点,以及缺乏有效的救治策略,使它成为人类健康的巨大威胁。免疫炎症反应失衡与脓毒症的发生发展密切相关,但其关键调控机制尚不清楚。微小RNA(micro RNA,mi RNA)在固有免疫反应和适应性免疫反应中起着重要作用。mi RNA通过调控炎症信号通路中关键分子的表达,从而影响脓毒症相关炎症因子的表达。因此,mi RNA可能成为在基因转录后水平诊断和治疗脓毒症的新靶点。     

Toll 样受体研究进展

Toll样受体（Toll－like receptors,TLRs）是新近发现的先天性免疫系统中的细胞跨膜受体及病原模式识别受体之一,在急性炎症反应细胞吞噬作用的调节和细胞信号转导及细胞凋亡中起重要作用,简要综述了Toll样受体的发现、分布、基因定位与结构特点、配体特异性及其介导的信号通路,并对其研究意义与前景作了简述。     

靶向 Toll 样受体的免疫调节剂研究进展

Toll 样受体是一类相对保守的模式识别受体,可以识别损伤相关分子模式和病原相关分子模式,从而启动天然免疫应答,在天然免 疫过程中发挥非常重要的作用。其介导的信号通路失调会引发各种炎症反应、癌症和自身免疫病等疾病。综述近年与 Toll 样受体有关的免 疫调节剂的研究进展,并概括与之相关的疾病,为靶向 Toll 样受体的免疫调节剂的研发提供一定参考。     

Toll样受体介导的肠道免疫研究进展

黏膜免疫系统的第一道防线——肠黏膜上皮,不但能区分和识别致病菌和共生菌,而且能启动适当的免疫应答。在机体正常情况下,肠黏膜上皮细胞（IEC）对肠道共生菌持耐受状态,维持肠道内环境的稳定。IEC能识别致病菌的危险信号,激活派伊尔结节,启动免疫应答。有关实验已证实肠黏膜上皮针对肠腔细菌呈“耐受”或“非耐受”状态,主要依赖于Toll样受体（TLRS）介导的信号转导通路。     

Toll样受体研究进展

Toll最早在果蝇中被发现。Toll受体蛋白（dToll）不仅参与果蝇胚胎发育时背腹的形成,而且参与成蝇对病原体侵袭的先天性免疫应答,是微生物诱导成年果蝇产生抗菌肽的信号转导通道的门户。Toll样受体是先天性模式识别受体,在细胞活化信号的转导中起重要作用。它作为联系先天性与获得性免疫系统的桥梁,备受人们关注。     

Toll样受体与肿瘤免疫

Toll样受体(Toll-like receptor)是天然免疫系统中最重要的模式识别受体,在病原体感染过程中对入侵病原体的识别,激活免疫应答起重要作用。近年发现Toll样受体在多种肿瘤的发生过程中起重要的调控作用。Toll样受体在肿瘤细胞中具有表达,并且Toll样受体信号诱导的促炎症反应是肿瘤发生的必要条件,但是有些Toll样受体的配体仍然表现出极强的抗肿瘤活性,目前,Toll样受体在肿瘤免疫中的机制研究已经成为Toll样受体作为药物靶点的临床应用的关键。本文对Toll样受体在肿瘤免疫中的机制进行综述。     

Toll样受体通路调节Tregs功能的研究进展

模式识别受体Toll样受体(Toll like receptors,TLRs)是固有免疫中免疫受体的代表,进化上十分保守,对生物体的生存极为重要。TLRs通过内源或外源的配体启动信号转导,激活下游一系列重要的基因表达与活化。研究表明调节性T细胞(Regulatory T cell,Treg)在维持机体外周免疫耐受和阻止移植排斥反应等方面发挥核心作用。Treg细胞表达某些TLRs,包括TLR2、TLR4、TLR5、TLR7、TLR8、TLR9等。TLRs的活化可能直接或间接地影响(主要是活化) Treg的增殖和免疫抑制功能,这种调节与感染、自身免疫病和癌症的发生密切相关。其中热休克蛋白作为TLRs配体分子对于Treg的调节发挥了重要的作用。因此,了解TLRs通路对研究Treg免疫调控机制、新药物研发和靶向治疗有重大意义。文中简要介绍了TLRs通路调节Treg免疫功能的相关研究进展。     

Toll样受体5基因多态性与中国人群脓毒症的相关性研究

目的探讨Toll样受体5（Toll-likereceptor5,TLR5）基因多态性位点与脓毒症发生风险及疾病严重程度的相关性。方法采用病例一对照研究设计,募集了255例脓毒症患者和260例对照个体。应用贝克曼公司的商用SNPstream分型技术和PCR—RFLP方法对TLR5基因的3个编码区多态性位点进行分型。采用Logistic回归分析,校正性别、年龄、吸烟和饮酒、慢性病状态、APACHEⅡ评分和脓毒症病因等混杂因素的影响,评价多态性位点与脓毒症的发生风险,以及脓毒症性休克、死亡和器官功能障碍等表型的遗传相关性。结果TLR5基因的3个多态性位点在病例和对照组中的基因型分布均呈哈．温平衡状态。这3个编码区的多态性位点与脓毒症的发生风险和疾病严重程度均无遗传学关联。结论TLR5基因的多态性位点可能在脓毒症的发生、发展和病程转归中不发挥重要作用。     

Toll样受体信号传导途径的研究进展

Toll样受体家族（Toll-like receptors,TLRs）成员在固有免疫反应,尤其是调节吞噬细胞（如巨噬细胞等）特异性识别微生物病原体抗原,分泌促炎细胞因子,上调共刺激分子,并诱导机体适应性免疫反应抗微生物病原体感染中发挥重要调控作用,被称为机体固有免疫和适应性免疫调节中的辅助受体（adjuvant receptor）。目前,对Toll样受体家族成员调控免疫反应信号传导途径的研究已成为分子免疫学领域的研究热点,认为主要存在髓样分化蛋白88（MyD88,是一种转接蛋白）依赖性和MyrD88非依赖性两条主要调控途径。本文仅就Toll样受体信号传导途径的研究进展作以简要综述。     

综述: MicroRNA与细胞信号通路的相互作用

MicroRNA(miRNA),广泛存在于多种生物中,在基因表达调控的转录后水平上发挥着重要的调节作用．细胞信号通路转导外界刺激进而引发一系列生理和病理效应,决定着细胞的功能和命运．而miRNA和细胞信号通路间的相互作用对于二者的功能发挥起着关键作用,本文将从信号通路对miRNA的调控和miRNA对信号通路的调节两方面综述二者的相互作用,揭示整合miRNA的细胞信号通路及其生物学意义．     

Disifin (Sodium tosylchloramide) and Toll-like receptors (TLRs): evolving importance in health and diseases

Disifin has emerged as a unique and very effective agent used in disinfection of wounds, disinfection of surfaces, materials and water, and other substances contaminated with almost every type of pathogenic microorganism ranging from viruses, bacteria, fungi and yeast, and, very possibly, protozoan parasites, as well. The major active component of Disifin is tosylchloramide sodium (chloramine T). However, the mechanism by which Disifin suppresses the activities of pathogenic microbial agents remains enigmatic. The molecular mechanisms, and the receptors and the signal transducing pathways responsible for the biological effects of Disifin are largely unknown. Despite considerable advances, enormous investigative efforts and large resources invested in the research on infectious diseases, microbial infection still remains a public health problem in many parts of the world. The exact nature of the pathogenic agents responsible for many infectious diseases, and the nature of the receptors mediating the associated inflammatory events are incompletely understood. Recent advances in understanding the molecular basis for mammalian host immune responses to microbial invasion suggest that the first line of defense against microbes is the recognition of pathogen-associated molecular patterns (PAMPs) by a family of transmembrane pattern-recognizing and signal transducing receptor proteins called Toll-like receptors (TLRs). The TLR family plays an instructive role in innate immune responses against microbial pathogens, as well as the subsequent induction of adaptive immune responses. TLRs mediate recognition and inflammatory responses to a wide range of microbial products and are crucial for effective host defense by eradication of the invading pathogens. Now, recent updates demonstrated the ability of Disifin-derived products, Disifin-Animal and Disifin-Pressant to effectively suppress the progression and activities of Chikungunya fever and that of avian influenza A virus [A/cardialis/Germany/72, H7N1: the agent of a highly pathogenic avian influenza (HPAI)] infection, respectively. Overall, the above findings led me to suggest that Disifin and TLRs may mechanistically overlap in the processes of executing their functions against pathogenic microbial organisms. Thus, elucidating and better understanding of the molecular underpinnings responsible for the biochemical effects of Disifin-products, and the nature and mode of the interaction(s) of Disifin with TLRs in the process of exerting their biological effects may open a novel dimension in the research of infectious diseases, which may provide novel therapeutic targets for the prevention and treatment of a wide range of infectious diseases.     

脓毒症分子机制及miRNA在脓毒症中的作用

脓毒症是外科重症监护病房(ICU)的主要死亡原因。近年来其发病呈上升趋势,且住院费用极昂贵,并缺乏有效的救治手段,已成为重症医学研究的重点。目前,关于脓毒症的发病机制并不清楚。研究表明,细胞内及细胞间多种信号通路如核因子κB(NF-κB)通路、丝裂原激活的蛋白激酶(MAPK)通路、JAK激酶/信号转导和转录激活子(JAK/STAT)通路、磷脂酰肌醇3激酶(PI3K/Akt)通路、胆碱能抗炎通路等及其下游的分子都参与脓毒症的发生发展。微小RNA(miRNA)作为小分子非编码RNA,通过转录后水平抑制靶基因的表达而参与细胞的多种过程。miRNA可以调控免疫细胞的分化及免疫反应,其不仅可以直接调控炎症因子的表达,还可作用于炎症信号传导通路的其他关键分子而间接调控脓毒症的发生发展。因此深入研究miRNA在脓毒症中的调节作用,可能为脓毒症的预防和治疗开拓新的思路。本文就参与脓毒症的信号通路及其下游分子以及miRNA进行总结,以利于进一步阐明脓毒症的病理生理机制,为脓毒症的预防和治疗找到合理有效的切入点。     

Dimerization of Toll-like Receptor 3 (TLR3) Is Required for Ligand Binding

TLR3 (Toll-like receptor 3) recognizes dsRNA, a potent indicator of viral infection. The extracellular domain of TLR3 dimerizes when it binds dsRNA, and the crystal structure of the dimeric complex reveals three sites of interaction on each extracellular domain, two that bind dsRNA and one that is responsible for dimer formation. The goal of this study was to determine which amino acid residues are essential for forming a stable receptor·ligand complex and whether dimerization of TLR3 is required for dsRNA binding. Using a novel ELISA to analyze dsRNA binding by mutant TLR3 constructs, we identified the essential interacting residues and determined that the simultaneous interaction of all three sites is required for ligand binding. In addition, we show that TLR3 is unable to bind dsRNA when dimerization is prevented by mutating residues in the dimerization site or by immobilizing TLR3 at low density. We conclude that dimerization of TLR3 is essential for ligand binding and that the three TLR3 contact sites individually interact weakly with their binding partners but together form a high affinity receptor·ligand complex.     

Toll样受体(TLRs)的信号转导与免疫调节

Toll样受体(Toll-like receptors,TLRs)是进化中比较保守的一个受体家族,至少包括10个成员.TLRs能特异地识别病原相关的分子模式(PAMPs),不仅在激活天然免疫中发挥重要的作用,而且还调节获得性免疫,是连接天然免疫和获得性免疫的桥梁.近年来,TLRs信号转导的研究,特别是在负调控研究领域,进展非常迅速.对TLRs信号通路新进展以及TLRs在抗感染免疫中的作用进行了综述.