title: Monocyte chemoattractant protein-1 selectively inhibits the acquisition of CD40 ligand-dependent IL-12-producing capacity of monocyte-derived dendritic cells and modulates Th1 immune response.
abstract: Accumulating evidence indicates that monocyte chemoattractant protein-1 (MCP-1), a CC chemokine, also displays immunoregulatory functions and may be involved in Th subset differentiation. In this study, we examined the effects of MCP-1 on the cytokine-driven differentiation of monocytes into dendritic cells (DCs), the most potent APCs for naive T cells. We found that DCs generated in the presence of MCP-1 displayed a markedly reduced production of IL-12 in response to CD40 ligand but not in response to Staphylococcus aureus stimulation in the presence or absence of IFN-gamma. The production of IL-10, a potent endogenous IL-12 inhibitor, was not affected by MCP-1. Whereas the inhibitory activity of MCP-1 on IL-12 production by monocytes was sensitive to pertussis toxin, its effects on DC differentiation were pertussis toxin resistant. MCP-1 did not affect the surface phenotype and T cell-stimulating activity of DCs, but most interestingly, naive T cells stimulated with MCP-1-primed DCs produced much less IFN-gamma but the same levels of IL-13. Taken together, our results indicated that MCP-1 modulates the differentiation of monocytes into DCs and may thereby inhibit Th1 cell development.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Fukui Medical University, Japan.
authors.forename: Nemuko
authors.initials: N
authors.lastname: Omata
authors.forename: Motoko
authors.initials: M
authors.lastname: Yasutomi
authors.forename: Akiko
authors.initials: A
authors.lastname: Yamada
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Mitsufumi
authors.initials: M
authors.lastname: Mayumi
authors.forename: Yusei
authors.initials: Y
authors.lastname: Ohshima
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000494:pharmacology*; D054407:Chemokine CCL4; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D007399:Interphase / Q000276:immunology; D007700:Kinetics; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D019013:CD40 Antigens; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D007166:Immunosuppressive Agents; D019402:Macrophage Inflammatory Proteins; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma; D037342:Pertussis Toxin