Oligosaccharide-dependent anti-inflammatory role of galectin-1 for macrophages in ulcerative colitis

Background and Aim: Galectin-1 plays a protective role against colitis by binding with polylactosamine structures on macrophages in beta-1,4-galactosyltransferase I-deficient mice, but the precise function of galectin-1 remains unknown. In the present study, we investigated the anti-inflammatory role of galectin-1 on macrophages to ameliorate ulcerative colitis in both animal model and human tissue samples. Methods: The expression of galectin-1 in colonic tissues of ulcerative colitis patients was evaluated by immtmohistochemistry. Cytokine production of mouse bone marrow-derived macrophages (BMDMs) cultured with galectin-1 was investigated. Galectin-1 binding capacity and polylactosamine expression in macrophages stimulated with lipopolysaccharides were evaluated by flow cytometry. BMDMs cultured with galectin-1 were transferred into Recombination activating gene (Rag) 2(-/)(-) mice, and the severity of the dextran sodium sulfate-induced colitis model was investigated. Furthermore, RNA sequencing was performed to characterize macrophages treated with galectin-1. Results: In ulcerative colitis patients, tissue expression of galectin- 1 was decreased in inflamed mucosa compared with non-inflamed mucosa. Galectin-1 induced interleukin-10 production in BMDMs, and the interleukin-10 production was abrogated by lactose, which inhibits the interaction of oligosaccharide-galectin binding. Dextran sodium sulfate colitis was significantly ameliorated in Rag2(-/-) mice undergoing galectin-1 -treated BMDM transfer compared with those undergoing vehicle-treated BMDM transfer. RNA sequencing revealed that treatment with galectin-1 increased the expression of CCAAT/enhancer binding protein p and CD163, but decreased the expression of CD80 on BMDMs. Conclusion: Galectin-1, whose expression is decreased in the inflamed mucosa of ulcerative colitis patients, can ameliorate murine colitis by conferring oligosaccharide-dependent anti-inflammatory properties to macrophages.