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Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Takasaki, Gunma, Japan
Dendritic cells (DC) that are stimulated with inflammatory
mediators can maturate and migrate from nonlymphoid tissues to lymphoid
organs to initiate T cell-mediated immune responses. This migratory
step is closely related to the maturation of the DC. In an attempt to
identify chemokine receptors that might influence migration and are
selectively expressed in mature DC, we have discovered that the
chemokine receptor, EBI1/CCR7, is strikingly up-regulated upon
maturation in three distinct culture systems: 1) mouse bone
marrow-derived DC, 2) mouse epidermal Langerhans cells, and 3) human
monocyte-derived DC. The EBI1/CCR7 expressed in mature DC is functional
because ELC/MIP-3ß, recently identified as a ligand of EBI1/CCR7,
induces a rise in intracellular free calcium concentrations and
directional migration of human monocyte-derived mature DC
(HLA-DRhigh, CD1alow, CD14-,
CD25+, CD83+, and CD86high) in a
dose-dependent manner, but not of immature DC (HLA-DRlow,
CD1ahigh, CD14-, CD25-,
CD83-, and CD86-). In contrast, macrophage
inflammatory protein-1
(MIP-1), monocyte chemotactic
protein-3 (MCP-3), and RANTES are active on immature DC but
not on mature DC. Thus, it seems likely that MIP-1, MCP-3, and
RANTES can mediate the migration of immature DC located in peripheral
sites, whereas ELC/MIP-3ß can direct the migration of Ag-carrying DC
from peripheral inflammatory sites, where DC are stimulated to
up-regulate the expression of EBI1/CCR7, to lymphoid organs. It is
postulated that different chemokines and chemokine receptors are
involved in DC migration in vivo, depending on the maturation state of
DC.
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H. Hasegawa, T. Nomura, M. Kohno, N. Tateishi, Y. Suzuki, N. Maeda, R. Fujisawa, O. Yoshie, and S. Fujita Increased chemokine receptor CCR7/EBI1 expression enhances the infiltration of lymphoid organs by adult T-cell leukemia cells Blood, January 1, 2000; 95(1): 30 - 38. [Abstract] [Full Text] [PDF]
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A.-S. Charbonnier, N. Kohrgruber, E. Kriehuber, G. Stingl, A. Rot, and D. Maurer Macrophage Inflammatory Protein 3{alpha} Is Involved in the Constitutive Trafficking of Epidermal Langerhans Cells J. Exp. Med., December 20, 1999; 190(12): 1755 - 1768. [Abstract] [Full Text] [PDF]
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H. D. Byrnes, H. Kaminski, A. Mirza, G. Deno, D. Lundell, and J. S. Fine Macrophage Inflammatory Protein-3{beta} Enhances IL-10 Production by Activated Human Peripheral Blood Monocytes and T Cells J. Immunol., November 1, 1999; 163(9): 4715 - 4720. [Abstract] [Full Text] [PDF]
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D. Yang, O. M. Z. Howard, Q. Chen, and J. J. Oppenheim Cutting Edge: Immature Dendritic Cells Generated from Monocytes in the Presence of TGF-{beta}1 Express Functional C-C Chemokine Receptor 6 J. Immunol., August 15, 1999; 163(4): 1737 - 1741. [Abstract] [Full Text] [PDF]
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J. G. Cyster Chemokines and the Homing of Dendritic Cells to the T Cell Areas of Lymphoid Organs J. Exp. Med., February 1, 1999; 189(3): 447 - 450. [Full Text] [PDF]
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R. M. Steinman and M. C. Nussenzweig Inaugural Article: Avoiding horror autotoxicus: The importance of dendritic cells in peripheral T cell tolerance PNAS, January 8, 2002; 99(1): 351 - 358. [Abstract] [Full Text] [PDF]
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