Liver sinusoidal endothelial cells — gatekeepers of hepatic immunity

Abstract

Liver sinusoidal endothelial cells (LSECs) line the low shear, sinusoidal capillary channels of the liver and are the most abundant non-parenchymal hepatic cell population. LSECs do not simply form a barrier within the hepatic sinusoids but have vital physiological and immunological functions, including filtration, endocytosis, antigen presentation and leukocyte recruitment. Reflecting these multifunctional properties, LSECs display unique structural and phenotypic features that differentiate them from the capillary endothelium present within other organs. It is now clear that LSECs have a critical role in maintaining immune homeostasis within the liver and in mediating the immune response during acute and chronic liver injury. In this Review, we outline how LSECs influence the immune microenvironment within the liver and discuss their contribution to immune-mediated liver diseases and the complications of fibrosis and carcinogenesis.

Immune-based therapies for hepatocellular carcinoma

“…LSECs are endowed with antigen-presenting capacity, being able to activate antigen specific CD4+ T-cell responses [13]. LSECs modulate immune cell recruitment through specific integrins (αLβ2, α4β1, α4β7) that facilitate capture, firm lymphocyte adhesion and subsequent chemotaxis mediated by pathways such as CXCL9-11/CXCR3, CXCL16/CXCR6 and CX 3 CL1/CX 3 CR1 [14]. In response to lipopolysaccharide (LPS), the prototypical PAMP molecule, the antigen-presentation capacity of LSECs is dampened by downregulation of constitutively expressed Major Histocompatibility Complex (MHC) class II, CD80 and CD86 molecules [15].…”

Sinusoidal Cells and Cytokine Response in the Tetrachloromethane-Induced Hepatotoxicity and an Approach to Its Correction

“…Изменения функционального состояния иммунокомпетентных клеток, к числу которых относятся синусоидальные клетки, оказывают существенное влияние на развитие патологических процессов в печени [16,17]. Результаты проведенного нами исследования подтверждают тот факт, что в ранние сроки токсического воздей-ТАБЛИЦА 1.…”

“…Синусоидальные эндотелиальные клетки являются многочисленной непаренхиматозной клеточной популяцией печени и представлены 4 основными разновидностями, имеющими мезенхимальное происхождение: лейкоциты, эндотелиоциты, клетки Ито, клетки Купфера или фиксированные макрофаги [12]. СК выполняют роль «барьера» в печеночных синусоидах, обеспечивают фильтрацию, эндоцитоз, презентацию антигенов и привлечение лейкоцитов к месту повреждения [17].…”

Updates in immunotherapy for hepatocellular carcinoma

“…Liver sinusoidal endothelial cells regulates the effector immune response by inhibiting CD4+ and CD8+ T lymphocytes, thus preventing an immune reaction against bacterial antigens coming from the gut. Moreover, these cells express high levels of Program death receptor ligand 1 (PD-L1), which is a transmembrane immunosuppressive protein that inactivates the adaptative immune system by binding to the inhibitory lymphocyte receptor PD-1 [16] .…”