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.
This project deals with natural killer (NK) cells which are immune cells that can kill cancer or infected cells. Much of what we know about NK cells comes from study of NK cells that circulate throughout the body. However, recent studies by the applicant show that certain organs, like the liver, contain large numbers of NK cells that do not recirculate and instead reside in the tissues. The current proposal will examine the fundamental properties of these cells in mice and humans to better understand how they participate in healthy and diseased individuals.
| Aw Yeang, Han Xian; Piersma, Sytse J; Lin, Yiing et al. (2017) Cutting Edge: Human CD49e- NK Cells Are Tissue Resident in the Liver. J Immunol 198:1417-1422 |
