title: Type I IFN regulate DC turnover in vivo.
abstract: 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 CD8alpha(+) 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 CD8alpha(+) 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.
authors: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy. fabrizio.mattei@iss.it
authors: Fabrizio
authors: F
authors: Mattei
authors: Laura
authors: L
authors: Bracci
authors: David F
authors: DF
authors: Tough
authors: Filippo
authors: F
authors: Belardelli
authors: Giovanna
authors: G
authors: Schiavoni
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007370:Interferon Type I / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D017471:Receptors, Interferon / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology; D051020:bcl-X Protein / Q000235:genetics
chemical_list: C494812:Bcl2l1 protein, mouse; D039521:CD11c Antigen; D016827:CD8 Antigens; C431698:CD8alpha antigen; D007370:Interferon Type I; D019253:Proto-Oncogene Proteins c-bcl-2; D017471:Receptors, Interferon; D051020:bcl-X Protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor