FG and TOC performed the experiments
FG and TOC performed the experiments. Imaging of Blood Flow Low-magnification (10) intravital video of the liver of a wild-type C57BL/6 animal (-)-Indolactam V during which fluorescent dextran was injected intravenously MAPK10 (red). Video is usually shown with no compression in time (i.e., at real time).(779 KB AVI). pbio.0030113.sv005.avi (779K) GUID:?E6063D41-C087-49C7-BAA3-DC6161EFD318 Video S6: NKT Cells Stop Patrolling upon Stimulation by ConA Low-magnification (10) intravital video of the liver of a animal during which 250 g of ConA was injected intravenously. Video is usually 300-fold compressed in time.(4.5 MB AVI). pbio.0030113.sv006.avi (4.4M) GUID:?FE51072D-4DEB-42A5-8D38-5B50DB08AAA3 Video S7: NKT Cells Stop Patrolling upon Stimulation by -GalCer Low-magnification (10) intravital video of the liver of a animal during which 5 g of -GalCer was injected intravenously. Video is usually 300-fold compressed in time.(7.5 MB AVI). pbio.0030113.sv007.avi (7.3M) GUID:?F74EA2B5-76A9-420A-AB63-4FD64A2A3D2E Video S8: Recruitment of Blood-Borne NKT Cell to Hepatic Sinusoidal Endothelium Low-magnification (10) intravital video of the liver of a animal taken at a high frame rate (1 frame/s). The arrival, initial rolling, and subsequent attachment and crawling of a single NKT is shown.(5.4 MB AVI). pbio.0030113.sv008.avi (5.2M) GUID:?2D123C1F-2E84-415F-94F4-9589C42B0A5C Abstract We examined the in vivo behavior of liver natural killer T cells (NKT cells) by intravital fluorescence microscopic imaging of mice in which a green fluorescent protein cDNA was used to replace the gene encoding the chemokine receptor CXCR6. NKT cells, which account for most CXCR6+ cells in liver, were found to crawl within hepatic sinusoids at 10C20 m/min and to (-)-Indolactam V stop upon T cell antigen receptor activation. CXCR6-deficient mice exhibited a selective and severe reduction of CD1d-reactive NKT cells in the liver and decreased susceptibility to T-cell-dependent hepatitis. CXCL16, the cell surface ligand for CXCR6, is usually expressed on sinusoidal endothelial cells, and CXCR6 deficiency resulted in reduced survival, but not in altered velocity or pattern of patrolling of NKT cells. Thus, NKT cells patrol liver sinusoids to provide intravascular immune surveillance, and CXCR6 contributes to liver-based immune responses by regulating their abundance. Introduction In both rodents and humans, the liver is the largest solid organ, and performs crucial immunological and metabolic functions. The liver receives nutrient-rich blood from the gut via the portal vein and oxygenated blood from the hepatic artery. It processes blood to remove toxins, synthesizes the majority of serum proteins and lipids, stores glycogen, and performs extensive lipid, cholesterol, and vitamin chemistry and storage. The liver is thought to provide a unique environment for lymphocytes, favoring tolerogenic immune system responses, possibly (-)-Indolactam V to prevent reactivity to harmless food antigens [1]. However, in response to certain stimuli, acute inflammatory reactions can occur, and result in hepatocyte death (hepatitis) and subsequent regeneration, with progressive fibrosis when stimuli are sustained. Several progressive liver diseases that can lead to liver failure have an autoimmune component [2]. The liver is an important site of visceral contamination. The low-pressure circulation and high surface area of contact between blood and parenchymal cells and the high phagocytic capacity of multiple cell types in liver provide pathogens with an easy route of access. The tolerizing environment may additionally contribute to immune avoidance. The World Health Organization estimates that approximately 5% and 3% of the world’s populace carry hepatitis B and hepatitis C computer virus, respectively [3]. Many of these cases result in chronic infections that can lead to fatal complications, including hepatocellular carcinoma, cirrhosis, or hemorrhage. Malaria and leishmania also display important liver tropisms [4,5]. Thus, immune surveillance of the liver for pathogens is an important, but poorly understood, process. The profile of steady-state hepatic immune cells differs markedly from that in secondary lymphoid organs and in other non-lymphoid tissues, with abundant Kupffer cells and natural killer T cells (NKT cells) supplemented with T cells, T cells, natural killer (NK) cells, dendritic cells, and few, if any, B cells. NKT cells, present at trace levels ( 1%) (-)-Indolactam V in many organs, are highly enriched in the liver, (-)-Indolactam V where they represent up to 30%.