肺脏基质细胞诱导不成熟树突状细胞为调节性树突状细胞的研究

发布时间：2018-06-10 10:02

本文选题：成纤维细胞样基质细胞 + 不成熟树突状细胞　；参考：《浙江大学》2006年硕士论文

【摘要】：树突状细胞(dendritic cell,DC)是机体内功能最强大的抗原提呈细胞(Antigen-presenting cells,APC),是免疫反应的启动者,因为它具有独特的刺激初始T细胞活化的能力而备受关注。但是随着对DC研究的深入,DC细胞群体的异质性越来越受到关注,DC不但可以启动免疫反应而且也能负向调控免疫反应。体内不但存在启动免疫反应的DC,同时也存在抑制免疫反应的DC。目前对调节性DC(Regulatory DC)的研究很多都是在体外进行的,如在原先的DC培养条件下加入各种免疫抑制性因子进而将造血前体细胞、成熟或不成熟DC诱导成具有负向调控作用的调节性DC,但这种方法过于简化,不能反映体内的真实情况,因而其诱导产生的DC可能就不一定代表体内的真实细胞亚群。机体是一个复杂的系统,各个组分在各个层次都可能发生相互作用,因此,免疫系统肯定也在各个层面受到其他系统的影响而更好发挥作用。我们以前的研究工作表明脾脏微环境无论对成熟DC或造血前体细胞都有重要的影响,脾脏基质细胞不但可以诱导造血前体细胞分化发育成为调节性DC,还可以诱导成熟DC进一步增殖分化成调节性DC。脾脏作为二级淋巴器官是免疫系统的一个组成部分,其微环境对免疫细胞的影响已经得到了一些阐明,那么其他实质器官如肺脏、肝脏、脑会不会也对免疫细胞具有同样的影响呢? 肺脏是机体最大的开放器官之一,每天肺脏都要接触大量的外界抗原,因此免疫耐受的形成对肺脏尤为重要。基质细胞(Stromal cells)作为器官的重要组分,除了其维持器官结构的功能外,它对免疫系统会有什么影响吗?有报道指出肺脏成纤维细胞与T细胞有比较紧密的联系,如成纤维细胞通过PGE2抑制T细胞的活化后死亡(activation induced cell death),那么肺脏基质细胞会对DC有什么影响吗?体外长期培养的细胞系可能有别于体内基质细胞组分,但仍然可以部分地模拟体内的微环境,而且细胞系使用方便,因此鉴于以上的思考,我们建立了小鼠的肺脏成纤维细胞样基质细胞系,通过该细胞系与DC的共培养体系来研究共培养后的DC的各种变化。
[Abstract]:Dendritic cell (DCC) is the most powerful antigen-presenting cell (APCP) in the body. It is the promoter of immune response and has attracted much attention because of its unique ability to stimulate the activation of initial T cells. However, with the further study of DC, the heterogeneity of DC cell population has attracted more and more attention. DC can not only initiate the immune response, but also negatively regulate the immune response. There are not only DCs that initiate immune response, but also DCs that inhibit immune response. At present, many studies on regulatory DCM are carried out in vitro, such as adding various immunosuppressive factors in the original DC culture condition, which will result in hematopoietic progenitor cells. Mature or immature DCs are induced into regulatory DCs with negative regulatory effects, but this method is too simplified to reflect the real situation in the body. So the DC that it induces may not necessarily represent a real subgroup of cells in the body. The body is a complex system in which the components may interact at all levels, so, The immune system must also be better affected by other systems at all levels. Our previous work has shown that spleen microenvironment has important effects on both mature DC and hematopoietic progenitor cells. Splenic stromal cells can not only induce the differentiation and development of hematopoietic precursor cells into regulatory DCs, but also induce the further proliferation and differentiation of mature DCs into regulatory DCs. The spleen, as a secondary lymphoid organ, is an integral part of the immune system. The effect of its microenvironment on immune cells has been elucidated. Does the brain have the same effect on immune cells? lung is one of the largest open organs of the body. Every day, the lungs are exposed to a large number of external antigens, so the formation of immune tolerance is particularly important to the lungs. Stromal cells (Stromal cells) as an important component of the organ, in addition to its function to maintain the organ structure, how does it affect the immune system? It has been reported that lung fibroblasts are closely related to T cells. If fibroblasts inhibit the activation of T cells through PGE2, then how do lung stromal cells affect DC? Cell lines that have been cultured for a long time in vitro may be different from the components of stromal cells in vivo, but they can still partly mimic the microenvironment in vivo, and the cell lines are easy to use. Therefore, in view of the above considerations, A mouse lung fibroblast-like stromal cell line was established. The co-culture system of the cell line and DC was used to study the changes of DC after co-culture.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R392

【引证文献】