Type I IFN regulate DC turnover in vivo.
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.
Mattei
Fabrizio
F
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy. fabrizio.mattei@iss.it
Bracci
Laura
L
Tough
David F
DF
Belardelli
Filippo
F
Schiavoni
Giovanna
G
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
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