脾脏在肺脏树突状细胞更新中的作用与机制研究

项目名称： 脾脏在肺脏树突状细胞更新中的作用与机制研究

项目编号： No.31470858

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 刘书逊

作者单位： 中国人民解放军第二军医大学

项目金额： 85万元

中文摘要： 肺脏树突状细胞(DC)各亚群分布在气道和肺间质不同位置，各司其职，确保肺脏对吸入的多样性抗原物质产生合适的免疫应答或耐受。肺脏髓系DC的分化起源、更新、生物学功能以及与肺部相关疾病的关系，目前还存在很多未知。前期研究发现，未成熟DC在脾脏基质微环境下再分化为F4/80+CD11b+CD103+单核样细胞，过继回输后可选择性定居于肺脏；脾切除小鼠肺脏F4/80+CD11b+CD103+细胞的更新明显被抑制，提示脾脏具有更新肺脏髓系DC的功能。在此基础上，我们拟深入探究脾脏是否通过诱导进入脾脏的DC表达CD103，从而参与更新肺脏髓系DC；阐明这群脾脏诱导DC来源的肺脏F4/80+CD11b+CD103+细胞的表型谱及其与已知肺脏DC的关系、肺脏定位、及其在气道Th2高反应性疾病中的作用，通过研究脾脏诱DC表达CD103的机制，解释脾脏对肺脏免疫功能的影响以及为肺部相关疾病的控制提供实验线索。

中文关键词： 脾脏基质微环境；肺脏树突状细胞；更新；过敏；CD103

英文摘要： Lung dendritic cell (DC) subsets have distinct locations in lung and bronchus，play distinct roles in lung immune response or immune tolerance in response to various inhaled antigenic substances.Up to date, the knowledge on the origins and development,replenishment and biological functions of lung myeolid DC subsets remains limited.Previous studies have demosntrated that immature DCs redifferentiated into CD103+ monocyte-like cells under splenic microenvironment, and these CD103+ monocyte-like cells selectively redistributed in lung after adaptively transferring; and in splenectomized mice, the replenishment of lung F4/80+CD11b+CD103+ was strongly inhibited, suggseting that spleen involves in replenishment of lung DCs. The present study intend to investigate whether spleen involves in replenishment of lung DCs via inducing redistribution of DCs migrating into spleen by inducible expression of CD103, the phenotype profile of the DC-derive spleen-induced lung F4/80+CD11b+CD103+ cells, its role in airway Th2 high response and the molecular mechanisms underlying inducible CD103 expression by spleen, through which provide an explanation to the effect of spleen on lung immunity and experimental evidence for controlling lung-related diseases.

英文关键词： splenic stromal microenvironment;lung dendritic cell;replenishment;allergy;CD103