系统性红斑狼疮患者miRNA异常在TLR7/9-IFN通路中的作用机制

系统性红斑狼疮（SLE）是一种复杂的以自身抗体大量产生为特点的慢性系统性自身免疫性疾病,发病机制尚未明确。近年来研究发现miRNA可通过多种方式参与SLE发病机制。本文重点阐述SLE患者miRNA异常对TLR7/9-IFN通路的影响,以利于进一步探讨SLE发病机制,为寻找新型靶向治疗药物提供思路。     

miRNA在系统性红斑狼疮患者T细胞中的作用及机制研究

miRNA为内源性非编码RNA,具有调控基因表达的能力,参与疾病过程.系统性红斑狼疮(systemic lupus erythe-matosus,SLE)是一种女性多发的全身性自身免疫性疾病,具有先天性免疫异常和获得性免疫异常的特点,其中T细胞功能异常在SLE的发病机制中发挥重要作用.研究发现,miRNA在SLE患者T...     

microRNA在系统性红斑狼疮中的作用及其机制的研究进展北大核心CSCD

系统性红斑狼疮(SLE)病因未明、发病机制复杂。microRNA(miRNA)是一类非编码RNA分子,通过与靶基因mRNA3'UTR相互作用,使靶基因mRNA降解或翻译抑制,作为转录后基因沉默的调控分子,miRNA调控的免疫细胞发育和功能异常与自身免疫病相关。研究证实多种miRNA与SLE发病及免疫功能异常密切相关,在SLE患者中表达上调或下调并与疾病活动度相关。研究表明miRNA可能通过以下方式参与SLE发病:1型干扰素通路;异常的炎性因子分泌;DNA低甲基化和组织炎症等。本文综述了miRNA与SLE发病之间的关系及作用机制研究进展。     

microRNA在系统性红斑狼疮中的作用及其机制的研究进展

系统性红斑狼疮(SLE)病因未明、发病机制复杂。microRNA(miRNA)是一类非编码RNA分子,通过与靶基因mRNA3'UTR相互作用,使靶基因mRNA降解或翻译抑制,作为转录后基因沉默的调控分子,miRNA调控的免疫细胞发育和功能异常与自身免疫病相关。研究证实多种miRNA与SLE发病及免疫功能异常密切相关,在SLE患者中表达上调或下调并与疾病活动度相关。研究表明miRNA可能通过以下方式参与SLE发病:1型干扰素通路;异常的炎性因子分泌;DNA低甲基化和组织炎症等。本文综述了miRNA与SLE发病之间的关系及作用机制研究进展。     

T细胞在系统性红斑狼疮中作用的研究进展

系统性红斑狼疮(SLE)是一累及多系统、多器官的自身免疫性疾病。大量自身抗体的产生和免疫复合物沉积在各组织、脏器中引起组织损伤是SLE的主要发病机制。而SLE中B细胞产生自身抗体呈T细胞依赖性，T细胞在SLE的发生发展中发挥重要作用。为阐明T细胞在SLE中的作用，首先需要了解SLE中T细胞的抗原识别特点和克隆扩增特点。     

神经精神性红斑狼疮的免疫学机制及其常用动物模型研究进展

系统性红斑狼疮(systemic lupus erythematosus,SLE)是以系统性、慢性、复发-缓解交替为特征的自身免疫性疾病典型代表,主要临床特点是血循环可检出大量自身抗体及多器官受损,其中神经精神性红斑狼疮(neuropsychiatric systemic lupus erythematosus,NPSLE)是常见并发症,患病率介于37%~95%之间,仅次于狼疮性肾炎,已成为影响SLE患者预后的主要因素之一[1]。目前NPSLE发病机制仍有很多未明之处,诊断与治疗仍面临很多挑战[2],加强NPSLE发病机制研究意义重大。本文将主要从神经免疫界面受损、免疫效应细胞、炎症因子、致病性自身抗体在NPSLE中发病作用研究进展及NPSLE研究常用动物模型进行综述,为阐明NPSLE发病机制和寻找研究靶点提供参考。     

神经精神性红斑狼疮的免疫学机制及其常用动物模型研究进展

系统性红斑狼疮(systemic lupus erythematosus,SLE)是以系统性、慢性、复发-缓解交替为特征的自身免疫性疾病典型代表,主要临床特点是血循环可检出大量自身抗体及多器官受损,其中神经精神性红斑狼疮(neuropsychiatric systemic lupus erythematosus,NPSLE)是常见并发症,患病率介于37%~95%之间,仅次于狼疮性肾炎,已成为影响SLE患者预后的主要因素之一[1]。目前NPSLE发病机制仍有很多未明之处,诊断与治疗仍面临很多挑战[2],加强NPSLE发病机制研究意义重大。本文将主要从神经免疫界面受损、免疫效应细胞、炎症因子、致病性自身抗体在NPSLE中发病作用研究进展及NPSLE研究常用动物模型进行综述,为阐明NPSLE发病机制和寻找研究靶点提供参考。     

硬皮病相关microRNA研究进展

硬皮病是一种以皮肤组织和内脏器官广泛纤维化、微血管改变和免疫反应异常为特征的复杂自身免疫性疾病,其发病机制尚不明确.近年来,较多研究结果显示硬皮病、类风湿和系统性红斑狼疮等自身免疫疾病具有类似的microRNA(miRNA)调控机制.进一步了解近年来自身免疫疾病中具有重要作用的miRNA以及硬皮病致病机制相关的miRNA可增进对其研究进展的理解.     

B淋巴细胞刺激因子及其拮抗剂与系统性红斑狼疮

B淋巴细胞刺激因子是B细胞生长、发育和分化中重要的免疫调控因子,其过度表达可能参与系统性红斑狼疮(systemiclupuserythematosus,SLE)发病机制中自身反应性B细胞的产生和自身免疫耐受的失衡。鉴于BlyS具有明显的B细胞趋向性,针对BLyS靶目标研制特异性抗体、相应受体或人可溶性BLyS结合小肽等,通过特异性封闭BLyS的免疫调控信号,拮抗其诱导的T、B淋巴细胞的高度活化和病理性自身抗体的产生,有望开辟一条治疗SLE等自身免疫病的新途径。     

免疫抑制疗法可调节系统性红斑狼疮患者的T淋巴细胞基因表达

系统性红斑狼疮(SLE)是一种自身免疫性疾病,它以B细胞功能亢进、能产生自身抗体和重要器官中有免疫复合沉积为特征.据报道,环境因素与疾病易感基因间复杂的相互作用可作为触发因素导致SLE发病.     

系统性红斑狼疮的分子遗传学研究

系统性红斑狼疮（systemiclupuserythematosus,SLE）是一种复合性多基因的自身免疫性疾病。遗传因素在SLE易感性方面起重要的作用。该文介绍目前已知几个与SLE的易感性有关的遗传基因。通过对这些基因研究,有利于阐明SLE的发病机制,进一步为SLE的预防、诊断和治疗提供重要的依据。     

Extracellular vesicles mediate intercellular communication: Transfer of functionally active microRNAs by microvesicles into phagocytes

Cell activation and apoptosis lead to the formation of extracellular vesicles (EVs) such as exosomes or microvesicles (MVs). EVs have been shown to modulate immune responses; recently, MVs were described to carry microRNA (miRNA) and a role for MVs in the pathogenesis of autoimmune diseases has been discussed. Here we systematically characterized MVs and exosomes according to their release stimuli. The miRNA content of viable or apoptotic human T lymphocytes and the corresponding MVs was analyzed. miRNA, protein and surface marker expression, as well as cytokine release by human monocytes was measured after EV engulfment. Finally, miRNA expression in T lymphocytes and MVs of healthy individuals was compared with those of systemic lupus erythematosus (SLE) patients. We demonstrate that, depending on the stimuli, distinct subtypes of EVs are released, differing in size and carrying a specific RNA profile. We observed an accumulation of distinct miRNAs in MVs after induction of apoptosis and the transfer of functional miRNA by MVs into human monocytes. MVs released from apoptotic cells provoke less of an inflammatory response than those released from viable cells. MiR‐155*, miR‐34b and miR‐34a levels in T lymphocytes and corresponding MVs were deregulated in SLE when compared to healthy individuals.     

Cutaneous lupus erythematosus: understanding of clinical features, genetic basis, and pathobiology of disease guides therapeutic strategies

Cutaneous features of the protean disease lupus erythematous (LE) constitute 4 of 11 diagnostic criteria for systemic lupus erythematosus (SLE) and are exhibited by approximately 3/4 of patients during the course of their disease. Because the pathogenesis of LE is multifactorial and polygenic, many of the details of the pathogenesis remain unclear. We review here the clinical features of cutaneous lupus and recent genetic data that elucidate potential candidate genes for both cutaneous lupus erythematosus (CLE) and SLE. We discuss advances in elucidating the autoimmune pathogenesis of CLE and SLE. Furthermore, promising experimental therapies based on these advances are reviewed in the context of B cell directed therapies, T cell directed therapies, disruption of B and T cell interactions, cytokine directed therapies and finally, end-effector targeted therapies.     

Cutaneous lupus erythematosus: Understanding of clinical features,genetic basis,and pathobiology of disease guides therapeutic strategies

Cutaneous features of the protean disease lupus erythematous (LE) constitute 4 of 11 diagnostic criteria for systemic lupus erythematosus (SLE) and are exhibited by approximately 3/4 of patients during the course of their disease. Because the pathogenesis of LE is multifactorial and polygenic, many of the details of the pathogenesis remain unclear. We review here the clinical features of cutaneous lupus and recent genetic data that elucidate potential candidate genes for both cutaneous lupus erythematosus (CLE) and SLE. We discuss advances in elucidating the autoimmune pathogenesis of CLE and SLE. Furthermore, promising experimental therapies based on these advances are reviewed in the context of B cell directed therapies, T cell directed therapies, disruption of B and T cell interactions, cytokine directed therapies and finally, end-effector targeted therapies.     

Gene expression profiling in the study of the pathogenesis of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a complex pathogenesis involving multiple genetic and environmental contributions. DNA microarray technology has recently been applied to unravel some of this complexity through genomewide profiling. Early studies using microarray analysis of peripheral blood mononuclear cells (PBMCs) from SLE patients revealed dysregulation of inflammatory cytokines, chemokines, and immune response-related genes, as well as genes involved in apoptosis, signal transduction, and the cell cycle. More recently, using arrays containing many more genes, 4 independent research groups have found that interferon (IFN)-regulated genes are highly overexpressed in the peripheral blood and kidney glomeruli of SLE patients, supporting a crucial role for interferon in SLE. Future studies focusing on target tissues or organs in lupus, including the kidney, may further contribute to our understanding of lupus pathogenesis while providing new targets for therapy.     

T cells in the pathogenesis of systemic lupus erythematosus

Recent studies in patients with systemic lupus erythematosus (SLE) have demonstrated that autoantigen-reactive T cells can be isolated from peripheral blood and that such cells can support autoantibody production ex vivo, suggesting that they may have a central role in the pathogenesis of disease. In addition, recent work has identified and characterized signaling abnormalities in T cells from SLE that may be fundamental to the disease. This review will examine the role of T cells in the pathogenesis of SLE and it will consider pathogenic mechanisms by which T cells escape normal of immunological tolerance. The focus will be on recent studies characterizing autoantigen-reactive human T cells and signaling abnormalities identified in T cells from patients with SLE.