自身免疫调节因子在免疫耐受形成中作用的研究进展

免疫耐受包括中枢免疫耐受和外周免疫耐受.中枢免疫耐受主要通过清除胸腺中能够识别自身抗原的自身反应性T细胞;而外周免疫耐受则是通过多种途径来消除外周成熟的自身反应性T细胞.自身免疫调节因子(autoimmune regulator,Aire)在中枢与外周免疫耐受建立和维持中起着举足轻重的作用,该单基因突变可引起自身免疫性疾病综合症.大量研究资料表明Aire可能成为临床诱导移植免疫耐受、抑制移植排斥反应、根治某些自身免疫性疾病的一个新靶点.     

组蛋白去乙酰化酶11的免疫调节机制研究进展

组蛋白的修饰作用是表观遗传学中的一个重要研究领域,组蛋白去乙酰化是组蛋白修饰的一个方面。组蛋白去乙酰化酶(histone deacetylases,HDACs)是一类催化脱去组蛋白赖氨酸上乙酰基的酶。HDACs在细胞免疫、染色质固缩和基因调控上起着关键作用。组蛋白去乙酰化酶11(histone deacetylase 11,HDAC11)作为HDACs第IV类中唯一的成员,与其它HDACs的特点和功能不尽相同,它与细胞免疫功能调节、免疫耐受、肿瘤发生、肾脏缺血再灌注损伤及神经系统发育等有着紧密的联系。本文就HDACs的分类及近几年所发现的HDAC11在免疫调节方面的作用做一综述。     

023 供体骨髓输注在肾脏移植耐受中的疗效和机制

同种移植免疫耐受的诱导和维持是控制移植后排斥反应,提高移植物存活的关键.动物实验及临床资料表明骨髓输注具有诱导免疫耐受的作用,其机制包括诱导T细胞无能,克隆清除,提供可溶性HLA抗原、抑制细胞及否决细胞,调节细胞表面分子及细胞因子,促进嵌合体的形成.因此,供体骨髓输注在诱导移植免疫耐受中具有相当的应用前景.     

免疫耐受的新认识与分子基础

目前研究发现免疫耐受产生机制的克隆排除学说存在着不少缺陷 ,学者们试图通过双信号、三信号及“danger”假说对其进行更正和完善。在这些假说中树突状细胞对免疫耐受发挥着举足轻重的作用 ,不同的树突状细胞将导致不同的免疫效应。某些新的分子如FasL和杀伤细胞抑制性受体在外周免疫耐受中的作用也日益受到关注 ,并成为治疗免疫性疾病及预防移植排斥的新靶点。     

蠕虫感染的免疫调节作用在诱导器官移植免疫耐受中应用价值的探讨

器官移植是重建器官功能的有效治疗方法,探寻无需长期服用免疫抑制的移植免疫耐受则是当前研究的热点。尽管几种诱导器官移植免疫耐受的方案已经被提出,甚至有些已应用于临床Ⅰ期试验,但这些免疫耐受诱导方案并没有达到理想的效果。本文从蠕虫感染能够长期调节宿主免疫反应的能力出发,从理论上阐明将蠕虫抗原用作调节受者免疫耐受的诱导的理论依据,提出受者免疫系统对供者移植器官的免疫耐受的形成需要供体抗原的刺激。输注供者脾脏来源的B淋巴细胞在联合蠕虫可溶性抗原作用下,让受者诱导供者特异性的免疫耐受具有重要的研究价值。     

雌二醇在诱导免疫耐受中的研究进展北大核心CSCD

移植排斥反应和自身免疫性疾病严重影响人类健康和生活质量,探寻其机制及应对策略一直是免疫耐受研究领域的重点问题。雌二醇是一类维持机体正常生理状态的重要激素,主要促进生殖系统发育,并对机体代谢水平进行调节。近年来,随着对免疫耐受的研究不断深入,雌二醇对免疫耐受的影响受到越来越多国内外学者的关注,大量研究显示,雌二醇在诱导免疫耐受中发挥重要作用。本文就雌二醇在诱导免疫耐受中的影响及其作用机制的研究现状进行综述,为诱导免疫耐受的研究提供新思路。     

供体骨髓输注在肾脏移植耐受中的疗效和机制

同种移植免疫耐受的诱导和维持是控制移植后排斥反应 ,提高移植物存活的关键。动物实验及临床资料表明 :骨髓输注具有诱导免疫耐受的作用 ,其机制包括诱导T细胞无能 ,克隆清除 ,提供可溶性HLA抗原、抑制细胞及否决细胞 ,调节细胞表面分子及细胞因子 ,促进嵌合体的形成。因此 ,供体骨髓输注在诱导移植免疫耐受中具有相当的应用前景     

T淋巴细胞与肝移植免疫耐受

背景：肝移植排斥反应的发病机制主要是T细胞介导的免疫应答,具有调节细胞功能的高活性、多功能的低分子蛋白质即细胞因子在器官移植排斥反应和免疫耐受中发挥着重要作用。目的：就T淋巴细胞与肝移植后免疫耐受的关系及研究现状作一综述。方法：由第一作者检索Medline 数据库及维普医学数据库1995年1月至2013年6月有关肝移植后免疫状态与T淋巴细胞及其细胞因子作用的文献。以“liver transplantation, immune tolerance, rejection, T lymphocytes”为英文检索词,“肝移植,排斥反应,免疫耐受,T淋巴细胞”为中文检索词,排除重复研究类文章。选取相关文献查找全文,纳入57篇,其中有关T淋巴细胞与移植后免疫状态研究背景的文献9篇,有关调节性T细胞在移植免疫中的作用10篇,有关T淋巴细胞与移植后免疫耐受关系的文献17篇,有关T淋巴细胞与移植后免疫耐受研究前景的文献21篇。结果与结论：T淋巴细胞是调节机体免疫应答一类重要的免疫细胞。接受同种异体肝移植后,受体发生免疫排斥还是免疫耐受与免疫系统中T淋巴细胞的亚群及其功能密切相关。通过阻断或诱导T淋巴细胞的某些功能可以诱导宿主免疫耐受。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

001 调节性T细胞与免疫耐受

近年来关于调节性T细胞在移植模型中介导免疫耐受的作用有相当大的进展.免疫调节的机制特别在感染性耐受途径中是通过调节性T细胞,包括Th2细胞因子(IL,-4、IL-10和TGF-β)均起着直接或间接的促进作用.胸腺是促进调节性T细胞产生的微环境.自身免疫性疾病模型中,调节性细胞有不同的胸腺来源的T细胞亚群.CD4+T细胞和CD8+T细胞都可调节免疫反应,诱导移植免疫耐受.     

调节性T细胞及其CD45亚群在肝移植免疫耐受中的相关研究

调节性T细胞(Tr)作为一种具有免疫抑制功能的细胞在器官移植免疫耐受中发挥了重要作用.它通过细胞接触抑制排斥反应发生、诱导移植免疫耐受,并且这种免疫抑制具有免疫过继作用.其中CD45亚群被认为是Tr中抑制功能较强的一群细胞,在移植免疫耐受中发挥着重要作用.而肝脏作为一种免疫特惠器官,与其他器官移植相比更易产生免疫耐受....     

Histone deacetylases 1 and 2 are expressed at distinct stages of neuro-glial development

The deacetylation of histone proteins, catalyzed by histone deacetylases (HDACs), is a common epigenetic modification of chromatin, associated with gene silencing. Although HDAC inhibitors are used clinically to treat nervous system disorders, such as epilepsy, very little is known about the expression pattern of the HDACs in the central nervous system. Identifying the cell types and developmental stages that express HDAC1 and HDAC2 within the brain is important for determining the therapeutic mode of action of HDAC inhibitors, and evaluating potential side effects. Here, we examined the expression of HDAC1 and HDAC2 in the murine brain at multiple developmental ages. HDAC1 is expressed in neural stem cells/progenitors and glia. In contrast, HDAC2 is initiated in neural progenitors and is up-regulated in post-mitotic neuroblasts and neurons, but not in fully differentiated glia. These results identify key developmental stages of HDAC expression and suggest transitions of neural development that may utilize HDAC1 and/or HDAC2.     

Spatiotemporal Expression of HDAC2 during the Postnatal Development of the Rat Hippocampus

Background: Histone acetylation, which is a chromatin modification of histone tails, can dynamically regulate the expression of various genes in normal development. HDAC2 is a negative regulatory factor of acetylation and closely related to learning and memory. NSE is a nerve marker and vital for maintaining physiological functions in nervous system. Currently, few studies associated with the expression pattern of HDAC2 in postnatal rat hippocampus have been reported. This study aimed to explore the temporal and spatial expression pattern of HDAC2, helping to reveal the expression characteristics of HDAC2 during postnatal neuronal maturation. Materials and Methods: With NSE as a biomarker of neuronal maturation at postnatal days 1, 3, 7 and weeks 2, 4, and 8 (P1D, P3D, P7D, P2W, P4W, P8W), the expression patterns of HDAC2 in rat hippocampus were examined using real-time PCR and western blotting. Additionally, the subcellular distribution of HDAC2 was analysed by immunofluorescence. Results: We found that HDAC2 was highly expressed in the neonatal period and decreased gradually. HDAC2 expression was widely distributed in neurons of hippocampal CA1, CA3 and DG regions and gradually shifted from the nucleus to the cytoplasm during postnatal development. Altogether, the expression of HDAC2 decreased gradually with different subcellular localizations throughout development. Conclusions: The observed results indicate that the expression levels of HDAC2 become lower and with different subcellular localizations in neurons during hippocampal neuronal maturation, suggesting the specific expression characteristics of HDAC2 might play an important role during postnatal learning-memory function and development.     

Epigenetic regulation of nervous system development by DNA methylation and histone deacetylation

Alterations in the epigenetic modulation of gene expression have been implicated in several developmental disorders, cancer, and recently, in a variety of mental retardation and complex psychiatric disorders. A great deal of effort is now being focused on why the nervous system may be susceptible to shifts in activity of epigenetic modifiers. The answer may simply be that the mammalian nervous system must first produce the most complex degree of developmental patterning in biology and hardwire cells functionally in place postnatally, while still allowing for significant plasticity in order for the brain to respond to a rapidly changing environment. DNA methylation and histone deacetylation are two major epigenetic modifications that contribute to the stability of gene expression states. Perturbing DNA methylation, or disrupting the downstream response to DNA methylation – methyl-CpG-binding domain proteins (MBDs) and histone deacetylases (HDACs) – by genetic or pharmacological means, has revealed a critical requirement for epigenetic regulation in brain development, learning, and mature nervous system stability, and has identified the first distinct gene sets that are epigenetically regulated within the nervous system. Epigenetically modifying chromatin structure in response to different stimuli appears to be an ideal mechanism to generate continuous cellular diversity and coordinate shifts in gene expression at successive stages of brain development – all the way from deciding which kind of a neuron to generate, through to how many synapses a neuron can support. Here, we review the evidence supporting a role for DNA methylation and histone deacetylation in nervous system development and mature function, and present a basis from which to understand how the clinical use of HDAC inhibitors may impact nervous system function.     

维甲酸诱导的小鼠神经管畸形模型中神经系统相关基因的表达情况分析

 摘要: 目的: 研究在全反式维甲酸诱导小鼠神经管畸形模型中神经系统相关基因（ASH2L,HDAC4,NSPC1与DOK5）的表达变化。方法: 取8只E8.5的C57/BL6孕鼠随机分为两组：对照组（4只），模型组（4只）。对照组腹腔注射橄榄油，模型组腹腔注射全反式维甲酸；E13.5取胚胎。采用Real-time PCR检测两组小鼠脑和脊髓中ASH2L,HDAC4,NSPC1与DOK5的mRNA表达；采用Western Blotting技术检测两组小鼠脑和脊髓中ASH2L,HDAC4,NSPC1与DOK5的蛋白表达情况。结果：全反式维甲酸可诱导小鼠出现典型神经管畸形；与对照组相比，全反式维甲酸处理组的致畸胚胎脑和脊髓中,ASH2L HDAC4, NSPC1和DOK5的mRNA表达有所下降（P<0.05）；同时这些基因的蛋白水平也显著下降 (P<0.05)。结论：ASH2L,HDAC4,NSPC1和DOK5可能是抑制全反式维甲酸致神经管畸形的潜在基因。