[Show abstract][Hide abstract]ABSTRACT: Galectin-9 Immunofluorescence in HCV liver. Paraffin embedded liver biopsy specimens were stained with antibodies to the proteins indicated and analyzed by confocal microscopy. A. Galectin-9/Albumin/DAPI staining. B. Galectin-9/CD68/DAPI staining. Double positive staining (yellow) indicated by white arrows. The white bar denotes 10 µm.
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[Show abstract][Hide abstract]ABSTRACT: Interferon-γ induces Galectin-9 mRNA in THP-1 cells. 106 THP-1 cells/ml were cultured in 20 ng/ml IFN-γfor the times indicated in triplicate. RNA was isolated, reverse transcribed and analyzed by TaqMan real time PCR using GAPDH as a control. P-values were calculated using a t-test.
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[Show abstract][Hide abstract]ABSTRACT: Approximately 200 million people throughout the world are infected with hepatitis C virus (HCV). One of the most striking features of HCV infection is its high propensity to establish persistence (approximately 70-80%) and progressive liver injury. Galectins are evolutionarily conserved glycan-binding proteins with diverse roles in innate and adaptive immune responses. Here, we demonstrate that galectin-9, the natural ligand for the T cell immunoglobulin domain and mucin domain protein 3 (Tim-3), circulates at very high levels in the serum and its hepatic expression (particularly on Kupffer cells) is significantly increased in patients with chronic HCV as compared to normal controls. Galectin-9 production from monocytes and macrophages is induced by IFN-gamma, which has been shown to be elevated in chronic HCV infection. In turn, galectin-9 induces pro-inflammatory cytokines in liver-derived and peripheral mononuclear cells; galectin-9 also induces anti-inflammatory cytokines from peripheral but not hepatic mononuclear cells. Galectin-9 results in expansion of CD4(+)CD25(+)FoxP3(+)CD127(low) regulatory T cells, contraction of CD4(+) effector T cells, and apoptosis of HCV-specific CTLs. In conclusion, galectin-9 production by Kupffer cells links the innate and adaptive immune response, providing a potential novel immunotherapeutic target in this common viral infection.