title: Systemic lupus erythematosus immune complexes increase the expression of SLAM family members CD319 (CRACC) and CD229 (LY-9) on plasmacytoid dendritic cells and CD319 on CD56(dim) NK cells.
abstract: Patients with systemic lupus erythematosus (SLE) display an activated type I IFN system due to unceasing IFN-α release from plasmacytoid dendritic cells (pDCs) stimulated by nucleic acid-containing immune complexes (ICs). NK cells strongly promote the IFN-α production by pDCs; therefore, we investigated surface molecules that could be involved in the pDC-NK cell cross-talk. In human PBMCs stimulated with RNA-containing ICs (RNA-ICs), the expression of the signaling lymphocyte activation molecule (SLAM) family receptors CD319 and CD229 on pDCs and CD319 on CD56(dim) NK cells was selectively increased. Upregulation of CD319 and CD229 on RNA-IC-stimulated pDCs was induced by NK cells or cytokines (e.g., GM-CSF, IL-3). IFN-α-producing pDCs displayed a higher expression of SLAM molecules compared with IFN-α⁻ pDCs. With regard to signaling downstream of SLAM receptors, pDCs expressed SHIP-1, SHP-1, SHP-2, and CSK but lacked SLAM-associated protein (SAP) and Ewing's sarcoma-activated transcript 2 (EAT2), indicating that these receptors may act as inhibitory receptors on pDCs. Furthermore, pDCs from patients with SLE had decreased expression of CD319 on pDCs and CD229 on CD56(dim) NK cells, but RNA-IC stimulation increased CD319 and CD229 expression. In conclusion, this study reveals that the expression of the SLAM receptors CD319 and CD229 is regulated on pDCs and NK cells by lupus ICs and that the expression of these receptors is specifically altered in SLE. These results, together with the observed genetic association between the SLAM locus and SLE, suggest a role for CD319 and CD229 in the SLE disease process.
authors: Section of Rheumatology, Department of Medical Sciences, Uppsala University, S-751 85 Uppsala, Sweden. niklas.hagberg@medsci.uu.se
authors: Niklas
authors: N
authors: Hagberg
authors: Jakob
authors: J
authors: Theorell
authors: Heinrich
authors: H
authors: Schlums
authors: Maija-Leena
authors: ML
authors: Eloranta
authors: Yenan T
authors: YT
authors: Bryceson
authors: Lars
authors: L
authors: Rönnblom
mesh_terms: D000936:Antigen-Antibody Complex / Q000276:immunology*; D015703:Antigens, CD / Q000096:biosynthesis*; D015153:Blotting, Western; D019002:CD56 Antigen / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D000071176:Signaling Lymphocytic Activation Molecule Family
chemical_list: D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D019002:CD56 Antigen; C430423:LY9 protein, human; C522918:NCAM1 protein, human; D011971:Receptors, Immunologic; C448987:SLAMF7 protein, human; D000071176:Signaling Lymphocytic Activation Molecule Family