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

Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan.

Gastroenterology 2012 May

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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. 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. 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. Altered oligosaccharide structures on immune cells modulate mucosal inflammation. Oligosaccharides in immune cells might be a therapeutic target for inflammatory bowel diseases. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Citation

Shinichiro Shinzaki, Hideki Iijima, Hironobu Fujii, Eri Kuroki, Norika Tatsunaka, Takahiro Inoue, Sachiko Nakajima, Satoshi Egawa, Tatsuya Kanto, Masahiko Tsujii, Eiichi Morii, Shunsaku Takeishi, Masahide Asano, Tetsuo Takehara, Norio Hayashi, Eiji Miyoshi. Altered oligosaccharide structures reduce colitis induction in mice defective in β-1,4-galactosyltransferase. Gastroenterology. 2012 May;142(5):1172-82