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.
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.
Omata
Nemuko
N
Department of Pediatrics, Faculty of Medicine, Fukui Medical University, Japan.
Yasutomi
Motoko
M
Yamada
Akiko
A
Iwasaki
Hiromichi
H
Mayumi
Mitsufumi
M
Ohshima
Yusei
Y
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
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