LIVER TISSUE-RESIDENT NATURAL KILLER CELLS

肝组织驻留自然杀伤细胞

• 批准号: 10116252
• 负责人: Wayne M. Yokoyama
• 金额: $ 18.76万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-19 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10116252
• 关键词: Acute; Biological Process; Blood; Cell Lineage; Cells; China; Collaborations; Data; Dependence; Development; Discontinuous Capillary; Disease; Goals; Hepatitis B Virus; Host Defense; Human; Immune; Immune response; Individual; Innate Immune System; Kidney; Knowledge; Laboratories; Laboratory Study; Lead; Liver; Malignant Neoplasms; Mediating; Mus; Mutant Strains Mice; Natural Killer Cells; Organ; Paper; Phenotype; Population; Primary carcinoma of the liver cells; Property; Publishing; Research; Research Personnel; Role; Skin; Skin Tissue; Spleen; Surface; Testing; Thymus Gland; Tissues; Uterus; Vascular System; Virus Diseases; Work; base; differential expression; experimental study; gut microbiota; insight; liver inflammation; liver injury; novel; pathogen; peripheral blood; phenotypic biomarker; preservation; professor; programs; response; transcription factor; tumor

Project Summary/Abstract This proposal is being submitted in response to RFA-AI-16-006, US-China Program for Biomedical Collaborative Research (USCPBCR) and is based on a long-standing collaboration between Professor Zhigang Tian (China) and Dr. Wayne Yokoyama (US). It concerns natural killer (NK) cells which are major components of the innate immune system providing host defense against pathogens and developing tumors. However, most of what is known about NK cells was derived from study of NK cells in mouse spleen and human peripheral blood. The collaborators found that the mouse liver contains two populations of NK cells, conventional NK (cNK) cells that resemble splenic NK cells and which circulate in the vascular system, and tissue-resident NK (trNK) cells that reside in the liver sinusoids. In published work, the investigators demonstrated that these cells form distinct NK cell lineages, based on phenotypic and functional analyses and transcription factor dependence. In preliminary studies, the investigators have identified a unique NK cell in the human liver which has properties of trNK cells found in mice, indicating that the concept of trNK cells is broadly applicable across species, suggesting that they have important, conserved biological functions. Thus, they propose the following Specific Aims to: 1) Study mouse liver trNK cells in sinusoids; 2) Determine role of mouse trNK cells in liver inflammation; and 3) Study human liver trNK cells. These studies will provide novel insight into the role of liver-resident NK cells and their contribution to host immune defense.

项目概要/摘要 本提案是为了响应 RFA-AI-16-006（中美生物医学计划）而提交的 合作研究 (USCPBCR) 是基于教授之间的长期合作 田志刚（中国）和韦恩横山博士（美国）。它涉及自然杀伤（NK）细胞，这是主要的 先天免疫系统的组成部分为宿主提供针对病原体和肿瘤发展的防御。 然而，关于 NK 细胞的大部分知识都来自对小鼠脾脏和小鼠脾脏中 NK 细胞的研究。 人类外周血。合作者发现小鼠肝脏含有两个 NK 细胞群， 传统 NK (cNK) 细胞类似于脾 NK 细胞，在血管系统中循环，以及 驻留在肝窦中的组织驻留 NK (trNK) 细胞。在已发表的作品中，研究人员 根据表型和功能分析，证明这些细胞形成不同的 NK 细胞谱系 转录因子依赖性。在初步研究中，研究人员发现了一种独特的 NK 细胞 人类肝脏具有小鼠中发现的 trNK 细胞的特性，这表明 trNK 细胞的概念很广泛 适用于跨物种，表明它们具有重要的、保守的生物学功能。因此，他们 提出以下具体目标： 1) 研究小鼠肝窦中的 trNK 细胞； 2）确定角色 小鼠 trNK 细胞在肝脏炎症中的作用； 3) 研究人类肝脏 trNK 细胞。这些研究将提供新颖的 深入了解肝脏驻留 NK 细胞的作用及其对宿主免疫防御的贡献。

项目成果

Cutting Edge: Human CD49e- NK Cells Are Tissue Resident in the Liver.

• DOI: 10.4049/jimmunol.1601818
• 发表时间: 2017-02-15
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Aw Yeang HX;Piersma SJ;Lin Y;Yang L;Malkova ON;Miner C;Krupnick AS;Chapman WC;Yokoyama WM
• 通讯作者: Yokoyama WM