LIVER TISSUE-RESIDENT NATURAL KILLER CELLS

肝组织驻留自然杀伤细胞

• 批准号: 9245783
• 负责人: Wayne M. Yokoyama
• 金额: $ 20万
• 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/9245783
• 关键词: Acute; Biological Process; Blood; Cell Lineage; Cells; China; Collaborations; Data; Dependence; Development; Discontinuous Capillary; Disease; Goals; Hepatitis B; Host Defense; Human; Immune; Immune response; Immunosuppressive Agents; 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; killings; liver inflammation; liver injury; novel; pathogen; peripheral blood; phenotypic biomarker; 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.

项目总结/摘要 本提案是根据RFA-AI-16-006《中美生物医学合作项目》提交的。 合作研究（USCPBCR），并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 天然免疫系统的组成部分提供宿主防御病原体和发展肿瘤。 然而，大多数关于NK细胞的知识来自于对小鼠脾脏中NK细胞的研究， 人外周血合作者发现小鼠肝脏含有两种NK细胞群， - 常规NK（cNK）细胞，其类似于脾NK细胞并且在血管系统中循环，以及 存在于肝窦中的组织驻留NK（trNK）细胞。在已发表的研究中， 证明这些细胞形成不同的NK细胞谱系，基于表型和功能分析， 转录因子依赖性在初步研究中，研究人员已经确定了一种独特的NK细胞， 人类肝脏具有在小鼠中发现的trNK细胞的特性，表明trNK细胞的概念是广泛的， 这表明它们具有重要的、保守的生物学功能。所以他们 提出以下具体目的：1）研究小鼠肝窦中的trNK细胞; 2）确定 小鼠肝脏炎症中的trNK细胞;和3）研究人肝脏trNK细胞。这些研究将提供新的 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。