Monocyte Stabilin-1 Suppresses the Activation of Th1 Lymphocytes

• Published in: The Journal of immunology (1950) 2016-01, Vol.196 (1), p.115-123
• Main Authors: Palani, Senthil, Elima, Kati, Ekholm, Eeva, Jalkanen, Sirpa, Salmi, Marko
• Format: Article
• Language: English
• Subjects: Base Sequence; Cell Adhesion Molecules, Neuronal - genetics; Cells, Cultured; Down-Regulation; Humans; Inflammation - immunology; Interferon-gamma - biosynthesis; Interleukin-4 - biosynthesis; Interleukin-5 - biosynthesis; Lymphocyte Activation - immunology; Macrophages - immunology; Monocytes - immunology; Oligonucleotide Array Sequence Analysis; Receptors, Lymphocyte Homing - genetics; RNA Interference; RNA, Small Interfering; Sequence Analysis, RNA; Th1 Cells - immunology; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1500257

In this study, we analyzed the putative functions of stabilin-1 in blood monocytes. Microarray analysis revealed downregulation of several proinflammatory genes in the stabilin-1(high) monocytes when compared with stabilin-1(low) monocytes. When cocultured with stabilin-1(high) monocytes, IFN-γ synthesis by T cells was diminished in Ag-recall assays. Knockdown of stabilin-1 in monocytes increased the synthesis of several proinflammatory molecules, including TNF-α, and supported high IFN-γ and low IL-4 and IL-5 production by T cells in Ag-specific stimulation assays. Anti-stabilin-1 Ab treatment also led to increased IFN-γ synthesis in the recall assays. In clinical settings, the expression of stabilin-1 was diminished on blood monocytes and tissue macrophages under proinflammatory conditions. These data define stabilin-1 as a new immunosuppressive molecule and suggest that stabilin-1(high) monocytes may dampen proinflammatory reactions in vivo.