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 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.