固有免疫在慢性阻塞性肺疾病发病机制中的作用

慢性阻塞性肺疾病(COPD)是气道慢性炎症性疾病,在炎症的启动及持续过程中,固有免疫的重要组成部分模式识别受体(PRRs)起到了重要作用.PRRs主要包括Toll样受体、NOD样受体、RIG-Ⅰ样受体.香烟烟雾、病原菌可以直接或间接通过损伤相关分子模式及病原体相关分子模式激活PRRs,使NF-κB依赖的促炎症基因表达,导致气道慢性炎症的形成及持续;此外,PRRs的先天情况也决定了 COPD的易感性.固有免疫反应产生的炎症介质与慢性支气管炎、COPD中肺泡的破坏、基质成分的降解及组织的重塑有关.本文主要讨论PRRs在COPD发生发展中的作用.     

模式识别受体 N O D2 在心血管疾病中的研究进展

核苷酸结合寡聚化结构域2(NOD2)属于NOD样受体家族,作为一种胞内模式识别受体,NOD2通过识别配体胞壁酰二肽参与宿主细胞对病原体的识别,介导免疫炎性反应。近年来研究发现,NOD2在心肌炎、动脉粥样硬化、心肌梗死等多种心血管疾病的发生发展过程中发挥重要作用。该文介绍NOD2在心血管疾病中的研究进展。     

天然免疫、Toll样受体与1型糖尿病

天然免疫在识别病原微生物后可迅速被激活,在免疫系统中起着非常重要的作用。天然免疫细胞通过表达不同的模式识别受体（PRRs）来识别病原体的信号分子。这些信号分子是天然免疫的重要组成部分,统称为病原相关分子模式（PAMPs）。至今已发现的PRRs包括Toll样受体（TLRs）、视黄酸诱导基因1（RIG-1）样受体（RLRs）和NOD样受体（NLRs）。     

肺炎中免疫反应的信号转导

肺上皮细胞、肺泡巨噬细胞、中性粒细胞和淋巴细胞均参与宿主对肺炎病原体的免疫反应。跨膜的Toll样受体（TLR）、核苷酸结合寡聚化结构域（NOD）样受体（NLR家族）、视黄酸诱导的基因样受体（RIG）-1（RLR家族）和A族巨噬细胞清道夫受体家族为识别病原体的受体。通过衔接蛋白,激活蛋白激酶、丝裂原活化的蛋白激酶（MAPK）、信号转导子及转录激活子（STAT）家族和核因子-κB（NF-κB）,诱导致炎细胞因子肿瘤坏死因子-α（TNF-α）等的表达及其它免疫反应。     

NLRP3介导炎症反应在心血管疾病中的研究进展

<正>1 NLRP3组成介绍1.1 NOD样受体(NLR)模式识别受体(PRR)是固有免疫中的免疫受体,其与病原微生物表面的病原体相关分子模式相互识别和作用是启动固有免疫应答的关键。目前已知的PRR有四种:NLRs、Toll样受体(TLR)、RIG样解旋酶(RLHs)和C型凝集素(CTL)。与TLR这个膜结合受体不同,NLR是一种丝氨酸/苏氨酸激酶,诱导细胞内病原体的先天免疫。到目前为     

NLRs家族成员NLRC5在免疫反应方面的研究进展

NOD样受体(NLRs)是细胞内感应器,能对各种不同的病原体和细胞内危险信号作出应答,从而诱导固有免疫反应。NLRC5是该家族成员之一,目前已经证实NLRC5是核转录因子κB、Ⅰ型干扰素、炎性体信号路径及MHC-Ⅰ基因表达的重要调节器,在固有免疫反应和适应性免疫反应中发挥举足轻重的作用。本文就的相关研究作一综述。     

慢性阻塞性肺疾病患者外周血单个核细胞NOD2 mRNA表达及白细胞介素-6的水平及意义

目的探讨外周血单个核细胞NOD2 mRNA和血清白细胞介素(IL)-6在慢性阻塞性肺疾病(COPD)发病机制中的作用及其与COPD患者严重程度的关系。方法对经过门诊及住院达到稳定期的COPD患者进行综合评估,分为A、B、C、D四组,每组30例,同期门诊健康体检者30例作为健康对照组,采用PCR和ELISA法分别检测COPD各组及健康对照组外周血单个核细胞核内NOD2 mRNA的表达及血清中IL-6的含量。结果 COPD稳定期患者外周血单个核细胞核内NOD2 mRNA及血清IL-6的表达均明显高于健康对照组(P<0.05)。COPD患者A、B、C、D各组中NOD2 mRNA和IL-6的表达明显高于健康对照组(P<0.05)。COPD患者D组NOD2 mRNA和IL-6的表达明显高于C组(P<0.05),C组和D组的NOD2 mRNA和IL-6的表达均明显高于A组和B组(P<0.05),A组和B组之间无统计学差异(P>0.05)。COPD患者NOD2 mRNA表达和IL-6的含量呈正相关(r=0.81,P<0.05)。结论 NOD2和IL-6都参与了COPD气道炎症的发生发展,其水平与COPD患者严重程度呈正相关。     

Toll样受体4与心血管疾病的研究进展

Toll样受体是一类表达于细胞膜上的受体家族,在先天性免疫和获得性免疫系统中,起到识别微生物的作用。Toll样受体4是最早发现的Toll样受体,在调节免疫应答、促进免疫细胞成熟分化和参与促炎因子反应中,都起到了重要作用。越来越多的研究证实,Toll样受体4作为先天性免疫的一个重要介质参与了心血管疾病的发生、发展。现主要对Toll样受体4在心血管疾病中的研究进展做一综述。     

Toll样受体和核苷酸结合寡聚蛋白2与克罗恩病

Toll样受体(TLR)和核苷酸结合寡聚蛋白2(NOD2)在结构上都富含亮氨酸重复序列(LRR),并在肠道黏膜的多种细胞表达,介导微生物与肠道黏膜之间的固有免疫反应。近年来研究发现,TLR和NOD2介导的免疫反应紊乱对克罗恩病的发生起重要作用。     

炎性小体与急性冠脉综合征的相关性

炎性小体是一类由凋亡相关微粒蛋白、半胱天冬酶（caspase）及 NOD 样受体组成的多蛋白复合物,它能介导 caspase-1活化,促进炎症因子白细胞介素（IL）-1β和IL-18前体成熟。该文主要介绍急性冠脉综合征与炎性小体相关性的研究进展。     

Pattern recognition receptors as potential therapeutic targets in metabolic syndrome: From bench to bedside

Pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs) play crucial roles in the underlying mechanisms of metabolic syndrome (MetS). Mainly, these receptors have been suggested to participate in the pathophysiological processes involved in the complications associated with this condition. Therefore, to evolve therapeutic strategies targeting PRRs might be an imperative approach to avoid the development of further complications in human subjects. In this work, we discuss the understanding regarding the roles of PRRs in the pathways of MetS to further describe potential advancements made to target these receptors within this pathology.     

Les inflammasomes et les maladies humaines

The understanding of the innate immunity, the first line of the host defence, was significantly modified following the sequential discovery of innate immune receptors such as the Toll-like receptors (TLRs) and the NOD-like receptors (NLRs). In response to recognition of microbial patterns or danger signals, some NLRs assemble a multimolecular platform termed as the inflammasome. Inflammasome assembly leads to the activation of the proinflammatory caspase-1. Consequently, an inflammatory immune response is mounted along with a programmed cell death, called pyroptosis. This review summarizes recent advances in the knowledge of the inflammasome and its role in auto-inflammatory diseases, autoimmune diseases, and most common metabolic, cardiovascular or rheumatic diseases.     

Inflammatory bowel disease: cause and immunobiology

Crohn's disease and ulcerative colitis are idiopathic inflammatory bowel disorders. In this paper, we discuss how environmental factors (eg, geography, cigarette smoking, sanitation and hygiene), infectious microbes, ethnic origin, genetic susceptibility, and a dysregulated immune system can result in mucosal inflammation. After describing the symbiotic interaction of the commensal microbiota with the host, oral tolerance, epithelial barrier function, antigen recognition, and immunoregulation by the innate and adaptive immune system, we examine the initiating and perpetuating events of mucosal inflammation. We pay special attention to pattern-recognition receptors, such as toll-like receptors and nucleotide-binding-oligomerisation-domains (NOD), NOD-like receptors and their mutual interaction on epithelial cells and antigen-presenting cells. We also discuss the important role of dendritic cells in directing tolerance and immunity by modulation of subpopulations of effector T cells, regulatory T cells, Th17 cells, natural killer T cells, natural killer cells, and monocyte-macrophages in mucosal inflammation. Implications for novel therapies, which are discussed in detail in the second paper in this Series, are covered briefly.     

Rôle de l’inflammasome dans les pathologies cardiovasculaires

NOD-like receptors (NLRs) constitute a recently identified family of intracellular pattern recognition receptors which contains more than 20 members in mammals. Some of the NLRs, the NALP subfamily, constituted from 14 members, many of them without actual identified role, form multiproteic complex known as inflammasome, that initiate inflammation by processing inactive pro-caspase-1 to its active form, allowing the cleavage and subsequent activation of pro-IL-1β and pro-IL-18. We review the identified roles of NLRs in pathologies and argue for the role of inflammasome in the development of cardiovascular diseases. The atherogenic cytokines IL-1β and IL-18 are matured in NLRPs inflammasomes. Immunocytochemistry shows that Nlrp3 inflammasome is expressed in plaques, upregulated and activated in the CD11b⁺Gr1^high atherosclerosis-prone monocyte subset and modulated by oxLDL in murine macrophages. These results provide an unexpected role for Nlrp3 inflammasome in atherosclerosis.     

Potential roles of nucleotide-binding oligomerization domain 2 in the pathogenesis of systemic lupus erythematosus

Nucleotide-binding oligomerization domain 2 (NOD2) is one of the most prominent member of the NOD-like receptors protein family that functions as intracellular pattern recognition receptors. Numerous studies have suggested the importance of NOD2 in defensing against microbial infections, regulation of the inflammatory process. It is shown that NOD2 contributes to the pathogenesis of various autoimmune and chronic inflammatory diseases, such as Crohn’s disease, rheumatoid arthritis. The aim of this study is to summarize our current understandings of NOD2 function and the role of NOD2 in systemic lupus erythematosus (SLE). The following databases were searched: Pubmed, EMBASE and Web of Science for English-language sources, using the terms “lupus,” “systemic lupus erythematosus,” ‘‘SLE,” “immunity,” “inflammatory” and “NOD2.” Emerging data evidences that NOD2 has important biological effects in autoimmunity and inflammatory and might take part in the pathogenesis of SLE. Studies exploring the relationship between NOD2 and SLE are very limited. Whether NOD2 could be a potentially valuable therapeutic target for treatment for SLE, more understanding of the mechanism of NOD2 is needed in the future in SLE.     

Role of the innate immune system in host defence against bacterial infections: focus on the Toll-like receptors

The innate immunity plays a critical role in host protection against pathogens and it relies amongst others on pattern recognition receptors such as the Toll-like receptors (TLRs) and the nucleotide-binding oligomerization domains proteins (NOD-like receptors, NLRs) to alert the immune system of the presence of invading bacteria. Since their recent discovery less than a decade ago, both TLRs and NLRs have been shown to be crucial in host protection against microbial infections but also in homeostasis of the colonizing microflora. They recognize specific microbial ligands and with the use of distinct adaptor molecules, they activate different signalling pathways that in turns trigger subsequent inflammatory and immune responses that allows a immediate response towards bacterial infections and the initiation of the long-lasting adaptive immunity. In this review, we will focus on the role of the TLRs against bacterial infections in humans in contrast to mice that have been used extensively in experimental models of infections and discuss their role in controlling normal flora or nonpathogenic bacteria. We also highlight how bacteria can evade recognition by TLRs.     

Ticagrelor and Dapagliflozin Have Additive Effects in Ameliorating Diabetic Nephropathy in Mice with Type-2 Diabetes Mellitus

Cardiovascular Drugs and Therapy - Ticagrelor and dapagliflozin can suppress the activation of the NOD-like receptor 3 (NLRP3)-inflammasome and activate AMP-activated protein kinase (AMPK). The...     

New aspects of the pathogenesis of gout. Danger signals, autoinflammation and beyond

Gout is caused by monosodium urate (MSU) crystal-induced inflammation of the joints and periarticular tissues. MSU crystals activate the NOD-like receptor (NLR) NALP3, which functions as a pattern recognition receptor (PRR). Activated NALP3 mediates interleukin-1b (IL-1b) generation from its inactive pro-form, resulting in the activation of further cells and an IL-8-mediated neutrophil influx into the joint. Based on these new findings on the pathophysiology of gout, an open pilot study has recently demonstrated successful treatment of gout with the soluble IL-1R antagonist anakinra in 10 patients. The physiological role of MSU crystals might be that of a danger signal in peripheral tissues, where they stimulate dendritic cell maturation. The role of PRRs such as the NLR is underlined by NALP3 mutations causing hereditary autoinflammatory syndromes and NOD2 polymorphisms as genetic risk factors for Crohn's disease. In addition to the recognition of danger-associated molecular patterns (e.g. MSU), PRRs confer autoantigen recognition and activation of the innate and adaptive immune system in autoimmune diseases. Detection of RNA and DNA-containing immune complexes by toll-like receptors inducing B-cell activation in systemic lupus erythematosus and of proteinase 3 by the protease-activated receptor-2 inducing dendritic cell maturation in Wegener's granulomatosis have recently been reported.     

The role of autoimmunity in gastroenterology

Crohn's disease (CD) is an immune-mediated chronic intestinal disorder thought to be the result of an aggressive immune response to a subset of enteric bacteria in a genetically predisposed host. Numerous environmental factors are apparently involved in disease pathogenesis. Impaired ability of CD patients to control the gut microflora is associated with defects in the production of some antibacterial compounds (cryptdins) by epithelial cells. In addition, there are the defects in cytoplasmic NOD-like receptors which are sensing intracellularly localized bacteria in CD patients. These defects together with the failure to induce autophagy lead to lack of bacterial clearance and subsequently to mucosal immunopathology.