Chemokine and chemokine receptor interactions provide a mechanism for selective T cell recruitment to specific liver compartments within hepatitis C-infected liver
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Colleges, School and Institutes
The role played by chemokines in regulating the selective recruitment of lymphocytes to different tissue compartments in disease is poorly characterized. In hepatitis C infection, inflammation confined to portal areas is associated with a less aggressive course, whereas T cell infiltration of the liver parenchyma is associated with progressive liver injury and cirrhosis. We propose a mechanism to explain how lymphocytes are recruited to hepatic lobules during bursts of necroinflammatory activity in chronic hepatitis C infection. We report here that lymphocytes infiltrating hepatitis C-infected liver express high levels of the chemokine receptors CCR5 and CXCR3. However, whereas the CCR5 ligands macrophage inflammatory protein-1alpha and -1beta were largely confined to vessels within portal tracts, the CXCR3 ligands IFN-inducible protein-10 and monokine-induced by IFN-gamma were selectively up-regulated on sinusoidal endothelium. In vitro, human hepatic sinusoidal endothelial cells secreted IFN-inducible protein-10 and monokine-induced by IFN-gamma in response to stimulation with IFN-gamma in combination with either IL-1 or TNF-alpha. This suggests that intrahepatic Th1 cytokines drive the increased expression of IFN-inducible protein-10 and monokine-induced by IFN-gamma and thereby promote the continuing recruitment of CXCR3-expressing T cells into the hepatic lobule in chronic hepatitis C infection.
|Number of pages||8|
|Journal||Journal of Immunology|
|Publication status||Published - 1 Dec 1999|
- Cell Movement, Chemokine CXCL10, Chemokine CXCL9, Chemokines, Chemokines, CXC, Endothelium, Vascular, Hepatitis C, Chronic, Humans, Intercellular Signaling Peptides and Proteins, Interferon-gamma, Kupffer Cells, Liver, Portal Vein, Receptors, CCR5, Receptors, CXCR3, Receptors, Chemokine, T-Lymphocyte Subsets, T-Lymphocytes, Th1 Cells, Th2 Cells, Tissue Distribution, Tumor Necrosis Factor-alpha