Core 2 Branching beta 1,6-N-Acetylglucosaminyltransferase and High Endothelial Venule-restricted Sulfotransferase Collaboratively Control Lymphocyte Homing

• Published in: The Journal of biological chemistry Vol. 279; no. 4; pp. 3058 - 3067
• Main Authors: Hiraoka, N, Kawashima, H, Petryniak, B, Nakayama, J, Mitoma, J, Marth, J D, Lowe, J B, Fukuda, M
• Format: Journal Article
• Language: English
• Published: 23.01.2004
• Subjects: L-selectin ligand sulfotransferase; lymphocyte homing
• DOI: 10.1074/jbc.M311150200
• ISSN: 0021-9258

L-selectin mediates lymphocyte homing by facilitating lymphocyte adhesion to carbohydrate ligands expressed on high endothelial venules (HEV) of the secondary lymphoid organs. Previous studies demonstrated that L-selectin ligand sulfotransferase (LSST) forms 6-sulfo sialyl Lewis x (sLe super(x)) on both core 2 branch and MECA-79-positive extended core 1 O-glycans, but the chemical nature and roles of HEV ligands elaborated by LSST and core 2 beta 1,6-N- acetylglucosaminyltransferase-1 (Core2GlcNAcT) have been undefined. In the present study, we have generated mutant mice with deficient LSST and show that inactivation of LSST gene alone leads to only partial impairment of lymphocyte homing to peripheral lymph nodes and moderate reduction in lymphocyte counts in the peripheral lymph nodes, despite the fact that L-selectin ligands that contain 6-sulfo sLe super(x) are reduced at HEV. By contrast, LSST/Core2GlcNAcT double null mice exhibited a markedly reduced lymphocyte homing and reduced lymphocyte counts as a result of significantly decreased 6-sulfo sLe super(x) on HEV L-selectin counterreceptors, relative to LSST- or Core2GlcNAcT-single null mice. Moreover, induction of LSST and Core2GlcNAcT transcripts was observed in HEV- like structure formed in the salivary gland of the non-obese diabetic mouse, which displays chronic inflammation. These results indicate that LSST and Core2GlcNAcT cooperatively synthesize HEV-specific L-selectin ligands required for lymphocyte homing and suggest that LSST and Core2GlcNAcT play a critical role in lymphocyte trafficking during chronic inflammation.