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Dendritic Cell Maturation Results in Pronounced Changes in Glycan Expression Affecting Recognition by Siglecs and Galectins¹

Marieke Bax^2,*, Juan J. García-Vallejo^2,*, Jihye Jang-Lee, Simon J. North, Tim J. Gilmartin, Gilberto Hernández, Paul R. Crocker, Hakon Leffler^¶, Steven R. Head, Stuart M. Haslam, Anne Dell and Yvette van Kooyk^3,*

^* Department of Molecular Cell Biology and Immunology, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands; Division of Molecular Biosciences, Imperial College, London, United Kingdom; DNA Microarray Core Facility, The Scripps Research Institute, La Jolla, CA 92037; Wellcome Trust Biocentre, University of Dundee, Dundee, United Kingdom; and ^¶ Section Microbiology, Immunology, and Glycobiology, Department of Laboratory Medicine, Lund University, Lund, Sweden

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported primarily by a Netherlands Organization of Scientific Research Pioneer grant (to Y.v.K.) and in part by National Institute of General Medical Sciences–The Consortium for Functional Glycomics GM62116. M.B. was supported by a Vrije Universiteit Medical Center Institute for Cancer and Immunology PhD student grant, P.R.C. was supported by the Wellcome Trust, and H. L. was supported by the Swedish Research Council. A.D. is a Biotechnology and Biological Sciences Research Council Professorial Fellow.

² M.B. and J.J.G.-V. contributed equally to this article.

³ Address correspondence and reprint requests to Dr. Y. van Kooyk, Department of Molecular Cell Biology and Immunology, Vrije Universiteit University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail address: y.vankooyk{at}vumc.nl

⁴ Abbreviations used in this paper: DC, dendritic cell; iDC, immature DC; mDC, mature DC; CLR, C-type lectin receptor; DC-SIGN, DC-specific ICAM-3-grabbing nonintegrin; MS, mass spectrometry; CRD, carbohydrate recognition domain; Ct, cycle threshold; Siglec, sialic acid-binding Ig superfamily lectin; MAA, Maackia amurensis agglutinin; SNA, Sambucus nigra agglutinin; RCA, Ricinus communis agglutinin.

⁵ The online version of this article contains supplemental material.

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