Oligosaccharide‐dependent anti‐inflammatory role of galectin‐1 for macrophages in ulcerative colitis. Issue 12 (6th July 2020) - Iwatani, Shuko
Abstract: Background and Aim: Galectin‐1 plays a protective role against colitis by binding with polylactosamine structures on macrophages in β‐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 immunohistochemistry. 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‐1was 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 β 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.