Altered Oligosaccharide Structures Reduce Colitis Induction in Mice Defective in beta-1,4-Galactosyltransferase

作者：Shinzaki Shinichiro; Iijima Hideki^*; Fujii Hironobu; Kuroki Eri; Tatsunaka Norika; Inoue Takahiro; Nakajima Sachiko; Egawa Satoshi; Kanto Tatsuya; Tsujii Masahiko; Morii Eiichi; Takeishi Shunsaku; Asano Masahide; Takehara Tetsuo; Hayashi Norio; Miyoshi Eiji

来源：Gastroenterology, 2012, 142(5): 1172-1182.

DOI：10.1053/j.gastro.2012.02.008

• IBD
• Mouse Model
• Immune Regulation
• CD

BACKGROUND %26 AIMS: Oligosaccharide modifications induce various functional changes in immune cells. The galactose-deficient fraction of fucosylated IgG oligosaccharides is increased, whereas that of beta-1,4-galactosyltransferase I (B4GalTI) is reduced, in patients with Crohn%26apos;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%26apos;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.

• 出版日期2012-5