Altered oligosaccharide structures reduce colitis induction in mice defective in β-1,4-galactosyltransferase

Abstract

Background & Aims: Oligosaccharide modifications induce various functional changes in immune cells. The galactose-deficient fraction of fucosylated IgG oligosaccharides is increased, whereas that of β-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 isolated from B4galt1+/- and B4galt1+/+ mice were adoptively 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. Results: Colitis induction by dextran sodium sulfate or trinitrobenzene sulfonic acid was significantly reduced in B4galt1+/- mice, which had galactose deficiency in IgG oligosaccharides (similar to patients with Crohn's disease) compared with B4galt1+/+ mice. Amelioration of colitis was associated with increased production of interleukin-10 by macrophages in B4galt1+/- mice. Colitis induction in recombination activating gene 2-/- mice by administration of CD4+CD62L+ T cells was reduced by cotransfer 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. © 2012 AGA Institute.