TGF-beta 1 reciprocally controls chemotaxis of human peripheral blood monocyte-derived dendritic cells via chemokine receptors

• Published in: The Journal of immunology (1950) Vol. 164; no. 5; pp. 2285 - 2295
• Main Authors: Sato, K, Kawasaki, H, Nagayama, H, Enomoto, M, Morimoto, C, Tadokoro, K, Juji, T, Takahashi, T A
• Format: Journal Article
• Language: English
• Published: United States 01.03.2000
• Subjects: CCR1 protein; CCR3 protein; CCR5 protein; CCR5 Receptor Antagonists; CCR6 protein; Cell Differentiation - immunology; Cell Membrane - metabolism; Cells, Cultured; Chemokine CCL19; Chemokine CCL20; Chemokines, CC - physiology; Chemotaxis, Leukocyte - immunology; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Down-Regulation - immunology; Humans; Immunophenotyping; Interleukin-10 - physiology; Ligands; macrophage inflammatory protein 3^a; Macrophage Inflammatory Proteins - physiology; Monocytes - immunology; RANTES; Receptors, CCR1; Receptors, CCR3; Receptors, CCR5 - biosynthesis; Receptors, CCR5 - metabolism; Receptors, CCR6; Receptors, CCR7; Receptors, Chemokine - antagonists & inhibitors; Receptors, Chemokine - biosynthesis; Receptors, Chemokine - metabolism; Receptors, Chemokine - physiology; Receptors, CXCR4 - antagonists & inhibitors; Receptors, CXCR4 - biosynthesis; Receptors, CXCR4 - metabolism; stromal cell-derived factor 1^a; Transforming Growth Factor beta - physiology; Transforming growth factor-^b1; Tumor Necrosis Factor-alpha - physiology; Up-Regulation - immunology
• ISSN: 0022-1767
• DOI: 10.4049/jimmunol.164.5.2285

We examined the effect of TGF-beta 1 on the chemotactic migratory ability of human monocyte-derived dendritic cells (DCs). Treatment of immature DCs with TGF-beta 1 resulted in increased expressions of CCR-1, CCR-3, CCR-5, CCR-6, and CXC chemokine receptor-4 (CXCR-4), which were concomitant with enhanced chemotactic migratory responses to their ligands, RANTES (for CCR-1, CCR-3, and CCR-5), macrophage-inflammatory protein-3 alpha (MIP-3 alpha) (for CCR-6), or stromal cell-derived growth factor-1 alpha (for CXCR-4). Ligation by TNF-alpha resulted in down-modulation of cell surface expressions of CCR-1, CCR-3, CCR-5, CCR-6, and CXCR-4, and the chemotaxis for RANTES, MIP-3 alpha, and stromal cell-derived growth factor-1 alpha, whereas this stimulation up-regulated the expression of CCR-7 and the chemotactic ability for MIP-3beta. Stimulation of mature DCs with TGF-beta 1 also enhanced TNF-alpha-induced down-regulation of the expressions of CCR-1, CCR-3, CCR-5, CCR-6, and CXCR-4, and chemotaxis to their respective ligands, while this stimulation suppressed TNF-alpha-induced expression of CCR-7 and chemotactic migratory ability to MIP-3 beta. Our findings suggest that TGF-beta 1 reversibly regulates chemotaxis of DCs via regulation of chemokine receptor expression.