Recruitment of lymphocytes to the human liver

Abstract

SummaryThis review discusses the function and localisation of lymphocytes resident within the human liver, under both physiological and pathological conditions. Through description of the mechanisms that mediate lymphocyte recruitment into tissues, this article explains how hepatic endothelial and epithelial cells regulate the recruitment of specific lymphocyte subpopulations. We illustrate that the expression of adhesion molecules and chemokines is crucial to the control of lymphocyte adhesion. Thus, in the normal liver, adhesion molecules such as vascular adhesion protein-1 (VAP-1), intercellular adhesion molecule-1 (ICAM-1) and intercellular adhesion molecule-2 (ICAM-2), and chemokines such as regulated on activation, normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), interferon γ inducible protein-10 (IP-10), MIG and interferon inducible T-cell alpha chemoattractant (ITAC) are involved in lymphocyte binding to different endothelial compartments. However, in response to inflammation or injury, additional expression of adhesion molecules such as VCAM-1, P-selectin and E-selectin, as well as higher levels of chemokines, permits the attraction and retention of specific effector populations of lymphocytes. We also discuss the expression and function of a newly defined adhesion protein, (VAP-1), and suggest that the unique functions of this protein may provide therapeutic potential for the treatment of liver disease.

Effective treatment of steatosis and steatohepatitis by fibroblast growth factor 1 in mouse models of nonalcoholic fatty liver disease

“…However, we did find a strong suppression of VCAM-1 expression in HUVEC endothelial cells. Sinusoidal endothelial cells play a major role in hepatic inflammation through their involvement in adhesion molecule-mediated recruitment of leukocytes (33). It was shown previously that FGF1 suppresses transendothelial leukocyte migration by reducing the expression of several endothelial adhesion molecules, including VCAM-1 (34).…”

Immune responses during acute and chronic infection with hepatitis C virus

“…IFN α/β produced by hepatocytes can induce the production of monocyte chemoattractant protein-1 (MCP-1) by the resident liver macrophages, which leads to the recruitment of other macrophages that produce macrophage inflammatory protein-1 alpha (MIP-1α). MIP-1α recruits NK cells, which in turn serve as a source of IFNγ; this cytokine may be antiviral but also leads to the production of monokine induced by IFNγ (MIG or CXCL9), which recruits T cells to the site of inflammation [172]. IFN-inducible protein-10 (IP-10), which correlates with the degree of inflammation, is also increased in chronic HCV [173].…”

Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines

“…Thus, T cell immigration into the liver is presumed to happen predominantly via the sinusoids. 3 Liver sinusoidal endothelial cells (LSEC) lining the sinusoids form a morphologically and functionally distinct endothelium that lacks a basement membrane, fails to form tight junctions, and displays fenestrae grouped to sieve plates. 4 In contrast to other tissues, selectins are not necessary for the initial adhesion of leukocytes to the liver microvasculature.…”

“…5 Subsequently, firm adhesion can occur through constitutively expressed adhesion molecules, such as intracellular adhesion molecule-1 6 and vascular adhesion protein-1 in humans. 3 Chemokines can activate integrins and support firm adhesion by binding lymphocyte integrins to the immunoglobulin superfamily adhesion molecules on the endothelial cell. Ultimately, cells leave the blood vessel and enter the extravascular tissue in response to chemokines.…”