N-acetylglucosamine-6-O-sulfotransferases 1 and 2 cooperatively control lymphocyte homing through L-selectin ligand biosynthesis in high endothelial venules

Nat Immunol. 2005 Nov;6(11):1096-104. doi: 10.1038/ni1259. Epub 2005 Oct 9.

Abstract

Lymphocyte homing is mediated by specific interactions between L-selectin on lymphocytes and sulfated carbohydrates restricted to high endothelial venules in lymph nodes. Here we generated mice deficient in both N-acetylglucosamine-6-O-sulfotransferase 1 (GlcNAc6ST-1) and GlcNAc6ST-2 and found that mutant mice had approximately 75% less homing of lymphocytes to the peripheral lymph nodes than did wild-type mice. Consequently, these mice had lower contact hypersensitivity responses than those of wild-type mice. Carbohydrate structural analysis showed that 6-sulfo sialyl Lewis X, a dominant ligand for L-selectin, was almost completely absent from the high endothelial venules of these mutant mice, whereas the amount of unsulfated sialyl Lewis X was much greater. These results demonstrate the essential function of GlcNAc6ST-1 and GlcNAc6ST-2 in L-selectin ligand biosynthesis in high endothelial venules and their importance in immune surveillance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Carbohydrate Sulfotransferases
  • Cell Movement
  • Dermatitis, Contact / enzymology
  • Dermatitis, Contact / genetics
  • Dermatitis, Contact / immunology
  • Endothelium, Lymphatic / immunology
  • Endothelium, Lymphatic / metabolism*
  • L-Selectin / metabolism*
  • Leukocyte Rolling*
  • Lewis X Antigen / analogs & derivatives
  • Ligands
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymphocytes / enzymology
  • Lymphocytes / immunology*
  • Mice
  • Mice, Knockout
  • Mucins / chemistry
  • Mucins / metabolism
  • Mutation
  • Oligosaccharides / analysis
  • Oligosaccharides / biosynthesis*
  • Sialyl Lewis X Antigen / analogs & derivatives
  • Substrate Specificity
  • Sulfotransferases / genetics
  • Sulfotransferases / metabolism*

Substances

  • 6'-sulfated sialyl Lewis x
  • Lewis X Antigen
  • Ligands
  • Mucins
  • Oligosaccharides
  • Sialyl Lewis X Antigen
  • L-Selectin
  • sulfated glycoprotein p50
  • Sulfotransferases