title: Altered oligosaccharide structures reduce colitis induction in mice defective in β-1,4-galactosyltransferase.
abstract: OBJECTIVE
  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.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Shinzaki
authors.forename: Hideki
authors.initials: H
authors.lastname: Iijima
authors.forename: Hironobu
authors.initials: H
authors.lastname: Fujii
authors.forename: Eri
authors.initials: E
authors.lastname: Kuroki
authors.forename: Norika
authors.initials: N
authors.lastname: Tatsunaka
authors.forename: Takahiro
authors.initials: T
authors.lastname: Inoue
authors.forename: Sachiko
authors.initials: S
authors.lastname: Nakajima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Egawa
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kanto
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tsujii
authors.forename: Eiichi
authors.initials: E
authors.lastname: Morii
authors.forename: Shunsaku
authors.initials: S
authors.lastname: Takeishi
authors.forename: Masahide
authors.initials: M
authors.lastname: Asano
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000032:analysis; D002450:Cell Communication; D003092:Colitis / Q000276:immunology / Q000517:prevention & control*; D005700:Galactosyltransferases / Q000502:physiology*; D037161:Galectins / Q000502:physiology; D016753:Interleukin-10 / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009844:Oligosaccharides / Q000737:chemistry / Q000502:physiology*
chemical_list: D039481:CD11b Antigen; D037161:Galectins; D009844:Oligosaccharides; D016753:Interleukin-10; D005700:Galactosyltransferases; C119701:beta-1,4-galactosyltransferase I