Nature Immunology 6, 1096 - 1104 (2005)
Published online: 9 October 2005; | doi:10.1038/ni1259
N-acetylglucosamine-6-O-sulfotransferases 1 and 2 cooperatively control lymphocyte homing through L-selectin ligand biosynthesis in high endothelial venulesHiroto Kawashima1, Bronislawa Petryniak2, Nobuyoshi Hiraoka1, Junya Mitoma1, Valerie Huckaby1, Jun Nakayama3, Kenji Uchimura4, Kenji Kadomatsu4, Takashi Muramatsu4, John B Lowe2
& Minoru Fukuda11
Glycobiology Program, Cancer Research Center, The Burnham Institute, La Jolla 92037, California, USA. 2
Howard Hughes Medical Institute, Life Sciences Institute, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. 3
Department of Pathology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan. 4
Department of Biochemistry, Nagoya University School of Medicine, Nagoya 466-8550, Japan.
Correspondence should be addressed to Minoru Fukuda minoru@burnham.org 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.
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