Interferon-γ switches monocyte differentiation from dendritic cells to macrophages

• Published in: Blood 2003-01, Vol.101 (1), p.143-150
• Main Authors: Delneste, Yves, Charbonnier, Peggy, Herbault, Nathalie, Magistrelli, Giovanni, Caron, Gersende, Bonnefoy, Jean-Yves, Jeannin, Pascale
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - analysis; Autocrine Communication; Biological and medical sciences; Bone Marrow Cells - cytology; Cell Culture Techniques - methods; Cell Differentiation - drug effects; Cytokines - pharmacology; Dendritic Cells - cytology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Regulation - drug effects; Hematopoietic Stem Cells - drug effects; Immunobiology; Immunophenotyping; Interferon-gamma - pharmacology; Interferon-gamma - physiology; Interleukin-6 - biosynthesis; Interleukin-6 - pharmacology; Macrophage Colony-Stimulating Factor - biosynthesis; Macrophage Colony-Stimulating Factor - drug effects; Macrophage Colony-Stimulating Factor - pharmacology; Macrophages - cytology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Modulation of the immune response (stimulation, suppression); Monocytes - cytology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-04-1164

Human monocytes differentiate into dendritic cells (DCs) or macrophages according to the nature of environmental signals. Monocytes stimulated with granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin 4 (IL-4) yield DCs. We tested here whether interferon-γ (IFN-γ), a potent activator of macrophages, may modulate monocyte differentiation. Addition of IFN-γ to IL-4 plus GM-CSF–stimulated monocytes switches their differentiation from DCs to CD14−CD64+macrophages. IFN-γ increases macrophage colony-stimulating factor (M-CSF) and IL-6 production by IL-4 plus GM-CSF–stimulated monocytes by acting at the transcriptional level and acts together with IL-4 to up-regulate M-CSF but not IL-6 production. IFN-γ also increases M-CSF receptor internalization. Results from neutralizing experiments show that both M-CSF and IL-6 are involved in the ability of IFN-γ to skew monocyte differentiation from DCs to macrophages. Finally, this effect of IFN-γ is limited to early stages of differentiation. When added to immature DCs, IFN-γ up-regulates IL-6 but not M-CSF production and does not convert them to macrophages, even in the presence of exogenous M-CSF. In conclusion, IFN-γ shifts monocyte differentiation to macrophages rather than DCs through autocrine M-CSF and IL-6 production. These data show that IFN-γ controls the differentiation of antigen-presenting cells and thereby reveals a new mechanism by which IFN-γ orchestrates the outcome of specific immune responses.