内皮型脾脏基质细胞诱导造血干细胞分化为调节性树突状细胞

发布时间：2018-02-16 05:36

本文关键词： 内皮型脾脏基质细胞造血干细胞分化调节性树突状细胞白细胞介素10 T细胞　出处：《浙江大学》2005年博士论文　论文类型：学位论文

【摘要】：树突状细胞(dendritic cells,DCs)是体内功能最强的抗原递呈细胞。在过去的十年中,多数研究者的兴趣是集中在DC是如何激发免疫应答的研究上,然而,近几年的工作显示DCs不但具有激发免疫反应的能力,而且,还可以下调免疫反应或者诱导免疫耐受的产生。现在普遍认为,DC在激活na(?)ve T细胞和诱导耐受中都扮演关键的角色。DCs既可以诱导中枢耐受又可以诱导外周耐受,特别是DCs在诱导外周耐受中的作用越来越受到重视。最近,具有免疫负向调节功能的调节性DCs(regulatory dendritic cells)被陆续发现,并成为这一研究领域的新热点。目前对调节性DCs的研究主要集中在对其起源和发育的研究上,所采用的方法多数是用免疫抑制性细胞因子诱导产生的,如在常规诱导DCs的培养基中加入IL-10或TGF-β。但这类方法过于简化,不能反映在体的实际分化过程,因此产生的DCs的特性是否能代表一种天然的细胞群体并不十分明确。造血细胞的体内发育过程是在一定的微环境的作用下进行的。所谓的微环境(microenvironment)或“龛位”(niche)是由成纤维细胞、巨噬细胞、内皮细胞、脂肪细胞等基质细胞和它们分泌的细胞外基质组成的,为造血细胞的发育提供各种必需的外源性信号的发育场所。不同的器官有不同的微环境,同一器官的不同区域的亚微环境也不同。不同的微环境可诱导产生不同的种类或功能特征的细胞。如骨髓的造血微环境。因此,脱离微环境来研究造血细胞的发育所得结论不可能反映机体的真实情况。脾脏是机体最大的外周免疫器官,又是哺乳动物的造血器官,并且小鼠脾脏终身保持造血功能。经典的脾结节形成实验证明,脾脏的微环境不但具有支持造血的作用,而
[Abstract]:Dendritic cells ( DCs ) are the most potent antigen - presenting cells in vivo . In the past decade , the interest of most researchers has been focused on how DCs can stimulate immune responses . However , recent studies have shown that DCs play a key role in activating na ( ? ) ve T cells and inducing tolerance . It is generally believed that DCs play a key role in activating na ( ? ) ve T cells and inducing tolerance . DCs can both induce central tolerance and induce peripheral tolerance , especially DCs in inducing peripheral tolerance . Recently , regulatory DCs with immune negative regulatory functions have been recognized . cells ) have been found in succession and become a new focus in this field of research . At present , the study of regulatory DCs is mainly focused on the study of the origin and development of DCs , most of which are induced by immunosuppressive cytokines , such as the addition of IL - 10 or TGF - 尾 in the culture medium of conventional induced DCs , but this method is too simplified to reflect the actual differentiation of DCs , and thus whether the nature of DCs produced represents a natural population of cells is not very clear . In vivo development of hematopoietic cells is carried out under the action of a certain microenvironment . The so - called microenvironment or niche consists of stromal cells , such as fibroblasts , macrophages , endothelial cells , fat cells , and extracellular matrix , and provides various necessary exogenous signals for the development of hematopoietic cells . Different organs have different microenvironment , and the sub - microenvironment of different regions of the same organ is different . The spleen is the largest peripheral immune organ of the organism , and is the hematopoietic organ of the mammal , and the spleen of the mouse keeps the hematopoietic function for a lifetime . The classical spleen nodule formation experiment proves that the microenvironment of the spleen not only has the function of supporting the hematopoietic function , but also

【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R392

【共引文献】