Type I IFN regulate DC turnover in vivo

• Published in: European journal of immunology 2009-07, Vol.39 (7), p.1807-1818
• Main Authors: Mattei, Fabrizio, Bracci, Laura, Tough, David F, Belardelli, Filippo, Schiavoni, Giovanna
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; bcl-X Protein - genetics; Blotting, Western; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; CD11c Antigen - metabolism; CD8 Antigens - metabolism; Cell Movement - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - metabolism; Female; Flow Cytometry; Gene Expression Regulation - drug effects; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Interferon Type I - administration & dosage; Interferon Type I - metabolism; Interferon Type I - pharmacology; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Proto-Oncogene Proteins c-bcl-2 - genetics; Receptors, Interferon - genetics; Receptors, Interferon - physiology; Reverse Transcriptase Polymerase Chain Reaction; Spleen - cytology; Turnover; Type I IFN
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200939233

DC are the most potent antigen-presenting cells that recognise signs of infection and serve as the main activators of naïve T cells. We have previously shown that type I IFN (IFN-I) are produced by DC and can act in an autocrine manner to activate DC. In the present study, we have investigated the role of IFN-I in regulating the turnover and lifespan of DC. We found that DC, especially the CD8α⁺ subset, from type I IFN receptor knock out (IFNAR KO) mice, display a reduced turnover rate when compared with DC from WT mice, as revealed by BrdU labelling kinetics. In vitro, IFNAR KO BM precursor cells cultured in the presence of GM-CSF generated CD11c⁺ DC less efficiently than WT BM, and the IFNAR KO DC that arose displayed reduced migratory ability. Interestingly, splenic DC from IFNAR KO mice exhibited a higher survival rate in short-term culture compared with control DC. Exposure to IFN-I in vivo markedly increased the turnover rate of splenic DC, particularly CD8α⁺ DC, which was preceded by a transient induction of apoptosis. In accordance with this, IFN-I stimulated the apoptosis of splenic DC in vitro. Overall, our data indicate that IFN-I are important regulators of DC turnover in vivo and suggest that these cytokines may exert this function through the modulation of multiple processes involving DC apoptosis, proliferation and migration.