Galectin-1 Restores Immune Tolerance to Liver Transplantation Through Activation of Hepatic Stellate Cells

Background/Aims: Immune tolerance is considered the only way to manage liver transplantation (LT). The current study hypothesized that galectin-1 via the activation of hepatic stellate cells (HSCs) is capable of inducing immune tolerance in LT. Methods: Lentiviral-mediated gene knockdown and overexpression of galectin-1 were conducted in HSC-T6 cells. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to determine galectin-1 expression. LT was performed in 20 C57BL/J6 mice and 20 C3H mice. T-cells were assigned into control, Galectin-1 shRNA, Galectin-1 OE, Galectin-1 OE SB431542, Galectin-1 OE Sulforaphane, Galectin-1 OE Y27632, and Galectin-1 OE U0126 groups. CFSE, flow cytometry, and ELISA were respectively employed to detect T-cell proliferation, CD4V CD8(+) ratio and IL-2, IL-10 and TGF-beta levels. After establishing mouse models of immune tolerance and acute rejection, immunohistochemistry, TUNEL, and immunofluorescence assay were performed to determine CD3(+) expression, apoptosis, alpha-SMA, and desmin. Mouse models of CCl4-induced liver fibrosis were established, followed by assigning the control, and CCl4 groups. ELISA was used to determine ALT, AST, TBIL and Hyp levels. A total of 3 C57BL/J6 mice (donor) and 6 C3H mice (recipient) were grouped into the control(2) and U0126 groups, followed by ELISA detection for IL-2, IL-10 and TGF-beta. Results: In T-cells, galectin-1 shRNA increased cell proliferation and IL-2 levels with reduced IL-10 and TGF-beta levels, while the Galectin-1 OE and Galectin-1 OE U0126 groups revealed the opposite results. Galectin-1 overexpression elevated the ratio of the CD4(+) to CD8(+) T-cells. The acute rejection group exhibited enhanced desmin expression and reduced alpha-SMA expression. Compared with the immune tolerance group, the acute rejection group displayed higher galectin-1 expression, a positive expression rate of CD3(+) T-cells, and an increased apoptosis rate. Compared with the control(1) group, the CCI4 group exhibited higher galectin-1 expression, ALT, AST, TBIL, and Hyplevels, alpha-SMA expression andCD4(+)/CD8(+) T-cell ratio, in addition to decreased expression of desmin. Compared with the control, group. U0126 increased galectin-1 expressions, IL-10 and TGF-beta levels and reduced IL-2 levels with inactivated HSCs. Conclusions: The findings of the current study indicated that the overexpression of galectin-1 promoted the activation of HSCs, which reduced the inflammatory response by exerting immunosuppressive effects and accordingly contributed to immune tolerance in LT. (C) 2018 The Author(s) Published by S. Karger AG, Basel