Characterization of Siglec-H as a novel endocytic receptor expressed on murine plasmacytoid dendritic cell precursors

Jiquan Zhang, Anna Raper, Noriko Sugita, Ravi Hingorani, Mariolina Salio, Michael J. Palmowski, Vincenzo Cerundolo, Paul R. Crocker

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    164 Citations (Scopus)

    Abstract

    We describe the cloning and characterization of Siglec-H, a novel murine CD33-related siglec-like molecule with 2 immunoglobulin domains. Unlike other CD33-related siglecs, Siglec-H lacks tyrosine-based signaling motifs in its cytoplasmic tail. Although Siglec-H has the typical structural features required for sialic acid binding, no evidence for carbohydrate recognition was obtained. Specific monoclonal and polyclonal antibodies (Abs) were raised to Siglec-H and used to define its cellular expression pattern and functional properties. By flow cytometry, Siglec-H was expressed specifically on plasmacytoid dendritic cell (pDC) precursors in bone marrow, spleen, blood, and lymph nodes. Staining of tissue sections showed that Siglec-H was also expressed in a subset of marginal zone macrophages in the spleen and in medullary macrophages in lymph nodes. Using bone marrow-derived pDC precursors that express Siglec-H, addition of Abs did not influence cytokine production, either in the presence or absence of synthetic oligodeoxynucleotides containing unmethylated cytosine-guanine motifs (CpG). In comparison, Siglec-H functioned as an endocytic receptor and mediated efficient internalization of anti–Siglec-H Abs. By immunizing mice with ovalbumin-conjugated anti–Siglec-H Ab in the presence of CpG, we demonstrate generation of antigen-specific CD8 T cells in vivo. Targeting Siglec-H may therefore be a useful way of delivering antigens to pDC precursors for cross-presentation.
    Original languageEnglish
    Pages (from-to)3600-3608
    Number of pages9
    JournalBlood
    Volume107
    Issue number9
    DOIs
    Publication statusPublished - May 2006

    Keywords

    • Dendritic cells
    • Hematopoietic stem cells
    • Plasma cells
    • Immunology
    • Metabolism
    • Receptors
    • Immunobiology

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    Zhang, J., Raper, A., Sugita, N., Hingorani, R., Salio, M., Palmowski, M. J., Cerundolo, V., & Crocker, P. R. (2006). Characterization of Siglec-H as a novel endocytic receptor expressed on murine plasmacytoid dendritic cell precursors. Blood, 107(9), 3600-3608. https://doi.org/10.1182/blood-2005-09-3842