Immunological functions of liver sinusoidal endothelial cells

Abstract

Liver sinusoidal endothelial cells (LSECs) line the liver sinusoids and separate passenger leukocytes in the sinusoidal lumen from hepatocytes. LSECs further act as a platform for adhesion of various liver-resident immune cell populations such as Kupffer cells, innate lymphoid cells or liver dendritic cells. In addition to having an extraordinary scavenger function, LSECs possess potent immune functions, serving as sentinel cells to detect microbial infection through pattern recognition receptor activation and as antigen (cross)-presenting cells. LSECs cross-prime naive CD8 T cells, causing their rapid differentiation into memory T cells that relocate to secondary lymphoid tissues and provide protection when they re-encounter the antigen during microbial infection. Cross-presentation of viral antigens by LSECs derived from infected hepatocytes triggers local activation of effector CD8 T cells and thereby assures hepatic immune surveillance. The immune function of LSECs complements conventional immune-activating mechanisms to accommodate optimal immune surveillance against infectious microorganisms while preserving the integrity of the liver as a metabolic organ.

Interleukin-33 drives hepatic fibrosis through activation of hepatic stellate cells

“…23,24 On binding to ST2 and IL-1 receptor accessory protein to form a trimeric complex, IL-33 activates T helper 2 (Th2) cell differentiation. 19 Further investigations revealed that IL-33 is host-protective against helminth infection and reduces atherosclerosis by promoting Th2-related immune responses. 25 However, IL-33 also exacerbates antigen-induced arthritis, and blockade of IL-33/ST2 signaling by soluble ST2 significantly attenuated allergic airway inflammation through the reduction of Th2-type cytokines, such as IL-5, IL-13 and IL-4.…”

“…Bile acid accumulation induced by BDL has been implicated in liver cytoplasmic membrane disintegration and oxidative stress, which might affect liver microenvironment and immune regulation. 19 HSC are pericytes found in the perisinusoidal space of the liver, and they are the principle source of ECM and collagen. 20,21 Abundant collagen production following liver damage and repair is the hallmark of liver fibrosis and cirrhosis, which may lead to portal hypertension and hepatic failure.…”

Wnt/β-Catenin Signaling in Liver Development, Homeostasis, and Pathobiology

“…Additionally, LSECs are efficient endocytic cells (164), allowing them to scavenge molecules from the blood and transport them to the hepatocyte surface (165). This process allows for more efficient delivery of metabolic compounds to the hepatocytes and also causes LSECs to function as sentinels for the hepatic acute phase response (166). LSECs express Toll-like receptors (TLRs) and can react to TLR ligands, such as bacterial-derived lipopolysaccharide (LPS) (167).…”

“…As LSECs are constantly bathed in bacterial degradation products from the portal venous blood, LSECs secrete inflammatory cytokines, such as interleukin-6 (IL-6), upon changes in LPS concentration (168). Secretion of IL-6 by LSECs promotes the hepatic acute phase response, in which hepatocytes secrete complement factors to help mount an innate immune response against infection (166). Thus, LSECs promote the metabolic function and health of a normal liver.…”

Directing Nanoparticle Biodistribution through Evasion and Exploitation of Stab2-Dependent Nanoparticle Uptake

“…11 Mammalian LSECs have also been implicated in clearance of blood-borne viruses from circulation 16−18 and are important cell-types of both the innate and adaptive immune system. 19,20 In LSECs, clearance function is mediated through a relatively small number of pattern-recognition endocytosis receptors. 11 Given the wide variety of macromolecules, colloids, and pathogens sequestered by LSECs, these receptors are clearly promiscuous with respect to potential binding partners.…”