Dendritic cell maturation results in pronounced changes in glycan expression affecting recognition by siglecs and galectins

Marieke Bax, Juan J. Garcia-Vallejo, Jihye Jang-Lee, Simon J. North, Tim J. Gilmartin, Gilberto Hernandez, Paul R. Crocker, Hakon Leffler, Steven R. Head, Stuart M. Haslam, Anne Dell, Yvette van Kooyk

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    Abstract

    Dendritic cells (DC) are the most potent APC in the organism. Immature dendritic cells (iDC) reside in the tissue where they capture pathogens whereas mature dendritic cells (mDC) are able to activate T cells in the lymph node. This dramatic functional change is mediated by an important genetic reprogramming. Glycosylation is the most common form of posttranslational modification of proteins and has been implicated in multiple aspects of the immune response. To investigate the involvement of glycosylation in the changes that occur during DC maturation, we have studied the differences in the glycan profile of iDC and mDC as well as their glycosylation machinery. For information relating to glycan biosynthesis, gene expression profiles of human monocyte-derived iDC and mDC were compared using a gene microarray and quantitative real-time PCR. This gene expression profiling showed a profound maturation-induced up-regulation of the glycosyltransferases involved in the expression of LacNAc, core 1 and sialylated structures and a down-regulation of genes involved in the synthesis of core 2 O-glycans. Glycosylation changes during DC maturation were corroborated by mass spectrometric analysis of N- and O-glycans and by flow cytometry using plant lectins and glycan-specific Abs. Interestingly, the binding of the LacNAc-specific lectins galectin-3 and -8 increased during maturation and up-regulation of sialic acid expression by mDC correlated with an increased binding of siglec-1, -2, and -7.

    Original languageEnglish
    Pages (from-to)8216-8224
    Number of pages9
    JournalJournal of Immunology
    Volume179
    Issue number12
    Publication statusPublished - 15 Dec 2007

    Keywords

    • Necrosis factor-alpha
    • DC-Sign
    • Inhibitory receptor
    • T-cells
    • Transcriptional regulation
    • Negative regulation
    • Phosphatases SHP-1
    • Molecular cloning
    • Immune responses
    • Trans-infection

    Cite this

    Bax, M., Garcia-Vallejo, J. J., Jang-Lee, J., North, S. J., Gilmartin, T. J., Hernandez, G., Crocker, P. R., Leffler, H., Head, S. R., Haslam, S. M., Dell, A., & van Kooyk, Y. (2007). Dendritic cell maturation results in pronounced changes in glycan expression affecting recognition by siglecs and galectins. Journal of Immunology, 179(12), 8216-8224. http://www.jimmunol.org/content/179/12/8216.full