组织微环境对人NK细胞程序性分化增殖的影响

项目名称： 组织微环境对人NK细胞程序性分化增殖的影响

项目编号： No.81330071

项目类型： 重点项目

立项/批准年度： 2014

项目学科： 医药、卫生

项目作者： 魏海明

作者单位： 中国科学技术大学

项目金额： 290万元

中文摘要： NK细胞有多种亚群，我们也利用 CD11b和CD27等分子将人NK细胞分为表型和功能不同的四个亚群。但随着研究的深入也出现新的科学问题：哪些微环境因素趋化NK细胞进入并定居在不同的组织或器官？哪些炎性因子在生理或病理状态时触发NK细胞的程序性分化和增殖？哪些转录因子直接调控NK细胞的功能及其与疾病的相关性？为了回答上述问题，我们将在前期工作的基础上进一步揭示微环境因素介导的NK细胞程序性增殖现象：1）分析体外环境中不同细胞因子组合促进CD34+造血干细胞分化为不同亚群NK细胞；2）分析组织生理和病理微环境中不同炎性因子组合促进未成熟NK细胞极化为不同功能NK细胞；3）进一步鉴定NK细胞在发育分化和功能极化过程中特异性转录因子的调控作用。籍此探明NK细胞的发育进程，特别是发生在微环境中的细胞因子诱导的、转录因子介导的NK细胞程序性增殖现象，从而弄清NK细胞在宿主防御和组织损伤中的双面角色。

中文关键词： 自然杀伤细胞;程序性增殖;功能;微环境;转录调控

英文摘要： Natural killer cells have been considered a heterogeneous population and may be divided into different subsets. We also characterized four novel populations defined by CD56, CD11b and CD27, which can represent the distinct stages of human NK cells from different tissues. Furthermore, we demonstrated that each population could be characterized by unique functional and phenotypic attributes. However, many new questions have arisen from our research. For example, which specific microenvironment elements allow for NK cells to locate in different tissue or organs? Can inflammatory cytokines trigger programmed differentiation and proliferation of NK cell during homeostasis and following infection? How transcription factors can directly modulate NK cell function and their pathogenic contribution to human diseases? Based on our extensive preliminary findings, we will indicate the programmed proliferation of NK cell after exposure to microenvironment elements. We will: 1) test a number of different cytokine combinations for their ability to support the proliferation and differentiation of human CD34+ hematopoietic stem cells (HSCs) into different NK cell populations; 2) test the hypothesis that inflammatory cytokines polarize the function of NK cell within solid organs in physiological and pathological microenvironment and 3) Further identify the specific transcription factors for the control of NK cell development and functions. It is to be hoped that research results in our understanding of the developmentally programmed and microenvironmentally driven functions of NK populations; particularly their cytokines production and transcriptional regulation, which shape the tissue microenvironment and contribute to host protection and tissue inflammation.

英文关键词： NK cell;programmed proliferation;function;Microenvironment;transcriptional regulation