Critical functions of N-glycans in L-selectin-mediated lymphocyte homing and recruitment

Junya Mitoma, Xingfeng Bao, Bronislawa Petryanik, Patrick Schaerli, Jean Marc Gauguet, Shin Yi Yu, Hiroto Kawashima, Hideo Saito, Kazuaki Ohtsubo, Jamey D. Marth, Kay Hooi Khoo, Ulrich H. von Andrian, John B. Lowe, Minoru Fukuda

Research output: Contribution to journalArticlepeer-review

162 Citations (Scopus)

Abstract

Lymphocyte homing is mediated by specific interaction between L-selectin on lymphocytes and the carbohydrate ligand 6-sulfo sialyl Lewis X on high endothelial venules. Here we generated mice lacking both core 1 extension and core 2 branching enzymes to assess the functions of O-glycan-borne L-selectin ligands in vivo. Mutant mice maintained robust lymphocyte homing, yet they lacked O-glycan L-selectin ligands. Biochemical analyses identified a class of N-glycans bearing the 6-sulfo sialyl Lewis X L-selectin ligand in high endothelial venules. These N-glycans supported the binding of L-selectin to high endothelial venules in vitro and contributed in vivo to O-glycan-independent lymphocyte homing in wild-type and mutant mice. Our results demonstrate the critical function of N-glycan-linked 6-sulfo sialyl Lewis X in L-selectin-dependent lymphocyte homing and recruitment.

Original languageEnglish
Pages (from-to)409-418
Number of pages10
JournalNature Immunology
Volume8
Issue number4
DOIs
Publication statusPublished - 2007 Apr
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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