Results Serum IgG of B 4 galt 1 / Mice Has an Agalactosyl Pattern Similar to That of Patients With CD B

g r c c BACKGROUND & AIMS: Oligosaccharide modifications induce various functional changes in immune cells. The galactose-deficient fraction of fucosylated IgG oligosaccharides is increased, whereas that of -1,4-galactosyltransferase I (B4GalTI) is reduced, in patients with Crohn’s disease. We investigated the role of oligosaccharide modification in the pathophysiology of colitis using B4galt1-deficient mice. METHODS: Colitis severity was compared between B4galt1 / and B4galt1 / mice. B cells solated from B4galt1 / and B4galt1 / mice were adopively transferred to recombination activating gene 2 / mice, in which colitis was induced by administration of CD4 CD62L T cells. Cell-surface glycan profiles were determined by lectin microarray analysis. Cytokine production was determined in a coculture of various types of cells isolated from either B4galt1 / or B4galt1 / mice. ESULTS: Colitis induction by dextran sodium sulfate or rinitrobenzene sulfonic acid was significantly reduced in 4galt1 / mice, which had galactose deficiency in IgG ligosaccharides (similar to patients with Crohn’s disease) ompared with B4galt1 / mice. Amelioration of colitis as associated with increased production of interleuin-10 by macrophages in B4galt1 / mice. Colitis induction in recombination activating gene 2 / mice by administration of CD4 CD62L T cells was reduced by otransfer of B cells isolated from B4galt1 / , but not from B4galt1 / mice. Lectin microarray analysis revealed increased expression of polylactosamines on B4galt1 / B cells and macrophages, compared with B4galt1 / cells. The production of interleukin-10 from macrophages was induced via their direct interaction with B4galt1 / B cells. CONCLUSIONS: Altered oligosaccharide structures on immune cells modulate mucosal inflammation. Oligosaccharides in immune cells might be a therapeutic target for inflammatory bowel diseases.

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