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.
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.
Authors: Mirna Šimurina; Noortje de Haan; Frano Vučković; Nicholas A Kennedy; Jerko Štambuk; David Falck; Irena Trbojević-Akmačić; Florent Clerc; Genadij Razdorov; Anna Khon; Anna Latiano; Renata D'Incà; Silvio Danese; Stephan Targan; Carol Landers; Marla Dubinsky; Dermot P B McGovern; Vito Annese; Manfred Wuhrer; Gordan Lauc Journal: Gastroenterology Date: 2018-01-06 Impact factor: 22.682
Authors: Xing Zhou; Francesca Motta; Carlo Selmi; William M Ridgway; M Eric Gershwin; Weici Zhang Journal: Autoimmun Rev Date: 2021-03-14 Impact factor: 9.754