LIVER TISSUE-RESIDENT NATURAL KILLER CELLS

项目摘要/摘要 本提案是为响应美国-中国生物医学计划RFA-AI-16-006而提交的 合作研究(USCPBCR)是建立在教授之间长期合作的基础上的 田志刚(中国)和横山博士(美国)。它涉及到自然杀伤(NK)细胞，这是主要的 先天免疫系统的组成部分，提供宿主防御病原体和发展肿瘤的能力。 然而，人们对NK细胞的了解大多来自对小鼠脾和脾中NK细胞的研究 人类外周血液。合作者发现，小鼠的肝脏含有两类NK细胞， 传统的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。在出版的作品中，调查人员 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。在初步研究中，研究人员发现了一种独特的自然杀伤细胞 人类肝脏具有在小鼠中发现的trNK细胞的特性，这表明trNK细胞的概念是广泛的 适用于所有物种，这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)研究小鼠肝脏trNK细胞在肝窦中的作用；2)确定 小鼠trNK细胞在肝脏炎症中的作用；3)研究人肝脏trNK细胞。这些研究将为我们提供新的 深入了解驻留在肝脏的NK细胞的作用及其对宿主免疫防御的贡献。

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.