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Monocyte Stabilin-1 Suppresses the Activation of Th1 Lymphocytes
Senthil Palani1, Kati Elima2, Eeva Ekholm3
1MediCity Research Laboratory, University of Turku, Turku 20520, Finland; Turku Doctoral Programme of Molecular Medicine, University of Turku, Turku 20520, Finland; Turku Doctoral Programme of Biomedical Sciences, University of Turku, Turku 20520, Finland;
Abstract:
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.
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