0000000000041462
AUTHOR
E. Löser
IL-10 down-regulates T cell activation by antigen-presenting liver sinusoidal endothelial cells through decreased antigen uptake via the mannose receptor and lowered surface expression of accessory molecules.
SUMMARYOur study demonstrates that antigen-presenting liver sinusoidal endothelial cells (LSEC) induce production of interferon-gamma (IFN-γ) from cloned Th1 CD4+ T cells. We show that LSEC used the mannose receptor for antigen uptake, which further strengthened the role of LSEC as antigen-presenting cell (APC) population in the liver. The ability of LSEC to activate cloned CD4+ T cells antigen-specifically was down-regulated by exogenous prostaglandin E2 (PGE2) and by IL-10. We identify two separate mechanisms by which IL-10 down-regulated T cell activation through LSEC. IL-10 decreased the constitutive surface expression of MHC class II as well as of the accessory molecules CD80 and CD86 …
Regulation of endotoxin-induced IL-6 production in liver sinusoidal endothelial cells and Kupffer cells by IL-10
SUMMARY Sinusoidal endothelial cells and Kupffer cells are the first cell populations in the liver that come into contact with gut-derived endotoxin in portal blood. Although endotoxin concentrations as high as 1 ng/ml are physiologically present in portal blood, no local inflammation is seen. We show that the proinflammatory cytokine IL-6, which is central to the development of inflammatory reactions in the liver, is produced by sinusoidal endothelial cells and Kupffer cells in response to low concentrations of endotoxin (100 pg/ml to 1 ng/ml). The anti-inflammatory cytokine IL-10 down-regulated endotoxin-induced IL-6 release in endothelial and Kupffer cells. Importantly, Kupffer cells sec…
Role of sinusoidal endothelial cells of the liver in concanavalin A-induced hepatic injury in mice
CD4+ T lymphocytes have been identified as being responsible for organ damage in the murine model of experimental liver injury induced by intravenous injection of concanavalin A (Con A). Liver sinusoidal endothelial cells (SEC) and Kupffer's cells (KC) are among the first cells that come into contact with lymphocytes in the liver sinusoid. We aimed to investigate the respective role of these cell populations in the initial steps of T-cell-mediated liver injury in Con A-induced hepatitis. By electron microscopy, we could show that intravenously applied Con A bound predominantly to SEC but not to KC. KC depletion by gadolinium chloride treatment of mice did not result in protection from liver…