TGF-beta 1 reciprocally controls chemotaxis of human peripheral blood monocyte-derived dendritic cells via chemokine receptors.
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.
Sato
K
K
Department of Cell Processing, AIDS Research Center, Institute of Medical Science, University of Tokyo, Japan.
Kawasaki
H
H
Nagayama
H
H
Enomoto
M
M
Morimoto
C
C
Tadokoro
K
K
Juji
T
T
Takahashi
T A
TA
D065100:CCR5 Receptor Antagonists; D002454:Cell Differentiation / Q000276:immunology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000502:physiology; D008024:Ligands; D019402:Macrophage Inflammatory Proteins / Q000502:physiology; D009000:Monocytes / Q000276:immunology; D054389:Receptors, CCR1; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000378:metabolism; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology
C515460:CCL19 protein, human; C108355:CCL20 protein, human; C515300:CCR1 protein, human; C515350:CCR3 protein, human; D065100:CCR5 Receptor Antagonists; C106311:CCR6 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D019742:Chemokines, CC; D008024:Ligands; D019402:Macrophage Inflammatory Proteins; D054389:Receptors, CCR1; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D054399:Receptors, CCR6; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10