title: Siglec-H is an IPC-specific receptor that modulates type I IFN secretion through DAP12.
abstract: Natural interferon (IFN)-producing cells are the primary cell type responsible for production of type I IFN in response to viruses. Herein we report the identification of the first molecular marker of mouse natural interferon-producing cells (IPCs), a novel member of the sialic acid-binding immunoglobulin (Ig)-like lectin (Siglec) family termed Siglec-H. Siglec-H is expressed exclusively on IPCs and is unique among Siglec proteins in that it associates with the adaptor protein DAP12. Moreover, we show that DAP12 modulates the type I IFN response of IPCs to a Toll-like receptor 9 (TLR9) agonist. This observation explains our previous finding that stimulation of IPCs with 440c, a Siglec-H-specific antibody, reduces IPC secretion of type I IFN. Moreover, it supports a model in which engagement of DNAX-activation protein 12 (DAP12)-associated receptors with antibodies or low avidity endogenous ligands interferes with TLR-mediated cellular activation.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Blasius
authors.forename: Marina
authors.initials: M
authors.lastname: Cella
authors.forename: Jorge
authors.initials: J
authors.lastname: Maldonado
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takai
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D001854:Bone Marrow Cells; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D037102:Lectins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology*; D051217:Toll-Like Receptor 9 / Q000819:agonists
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D007370:Interferon Type I; D037102:Lectins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C510552:Siglech protein, mouse; D051217:Toll-Like Receptor 9; C484963:Tyrobp protein, mouse