title: Activation of natural killer T cells by alpha-galactosylceramide in the presence of CD1d provides protection against colitis in mice.
abstract: OBJECTIVE
  CD1d is a major histocompatibility complex class I-like molecule that presents glycolipid antigens to a subset of natural killer (NK)1.1(+) T cells. These NK T cells exhibit important immunoregulatory functions in several autoimmune disease models.
  
  
  METHODS
  To investigate whether CD1d and NK T cells have a similar role in intestinal inflammation, the effects of the glycolipid, alpha-galactosylceramide (alpha-GalCer), on dextran sodium sulfate (DSS)-induced colitis were examined. Wild-type (WT), CD1d(-/-), and RAG(-/-) mice were examined for their response to either alpha-GalCer or the control analogue, alpha-mannosylceramide (alpha-ManCer).
  
  
  RESULTS
  WT mice, but not CD1d(-/-) and RAG(-/-) mice, receiving alpha-GalCer had a significant improvement in DSS-induced colitis based on body weight, bleeding, diarrhea, and survival when compared with those receiving alpha-ManCer. Elimination of NK T cells through antibody-mediated depletion resulted in a reduction of the effect of alpha-GalCer. Furthermore, adoptive transfer of NK T cells preactivated by alpha-GalCer, but not alpha-ManCer, resulted in diminished colitis. Using a fluorescent-labeled analogue of alpha-GalCer, confocal microscopy localized alpha-GalCer to the colonic surface epithelium of WT but not CD1d(-/-) mice, indicating alpha-GalCer binds CD1d in the intestinal epithelium and may be functionally active at this site.
  
  
  CONCLUSIONS
  These results show an important functional role for NK T cells, activated by alpha-GalCer in a CD1d-restricted manner, in regulating intestinal inflammation.
authors.affiliation: Division of Gastroenterology and the Harvard Digestive Diseases Center, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Saubermann
authors.forename: P
authors.initials: P
authors.lastname: Beck
authors.forename: Y P
authors.initials: YP
authors.lastname: De Jong
authors.forename: R S
authors.initials: RS
authors.lastname: Pitman
authors.forename: M S
authors.initials: MS
authors.lastname: Ryan
authors.forename: H S
authors.initials: HS
authors.lastname: Kim
authors.forename: M
authors.initials: M
authors.lastname: Exley
authors.forename: S
authors.initials: S
authors.lastname: Snapper
authors.forename: S P
authors.initials: SP
authors.lastname: Balk
authors.forename: S J
authors.initials: SJ
authors.lastname: Hagen
authors.forename: O
authors.initials: O
authors.lastname: Kanauchi
authors.forename: K
authors.initials: K
authors.lastname: Motoki
authors.forename: T
authors.initials: T
authors.lastname: Sakai
authors.forename: C
authors.initials: C
authors.lastname: Terhorst
authors.forename: Y
authors.initials: Y
authors.lastname: Koezuka
authors.forename: D K
authors.initials: DK
authors.lastname: Podolsky
authors.forename: R S
authors.initials: RS
authors.lastname: Blumberg
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics / Q000494:pharmacology*; D055610:Antigens, CD1d; D003092:Colitis / Q000139:chemically induced / Q000517:prevention & control*; D016264:Dextran Sulfate; D005699:Galactosylceramides / Q000493:pharmacokinetics / Q000494:pharmacology*; D016654:Genes, RAG-1 / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D020033:Protein Isoforms / Q000493:pharmacokinetics / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; D005699:Galactosylceramides; D020033:Protein Isoforms; D016264:Dextran Sulfate