Loss of type I IFN receptors and impaired IFN responsiveness during terminal maturation of monocyte-derived human dendritic cells.
Type I IFNs are modulators of myeloid dendritic cell (DC) development, survival, and functional activities. Here we monitored the signal transduction pathway underlying type I IFN biological activities during in vitro maturation of human monocyte-derived DCs. IFN-inducible tyrosine phosphorylation of STAT family members was severely impaired upon LPS-induced DC maturation. This correlated with a marked reduction of both type I IFN receptor chains occurring as early as 4 h after LPS treatment. The reduced receptor expression was a post-transcriptional event only partially mediated by ligand-induced internalization/degradation. In fact, although an early and transient production of type I IFNs was observed after LPS treatment, its neutralization was not sufficient to completely rescue IFN receptor expression. Notably, neutralization of LPS-induced, endogenous type I IFNs did not interfere with the acquisition of a fully mature surface phenotype, nor did it have a significant effect on the allostimulatory properties of LPS-stimulated DCs. Overall, these data indicate that DCs strictly modulate their responsiveness to type I IFNs as part of their maturation program, underlining the importance of the IFN system in the regulation of DC physiology.
Gauzzi
Maria Cristina
MC
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
Canini
Irene
I
Eid
Pierre
P
Belardelli
Filippo
F
Gessani
Sandra
S
D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007370:Interferon Type I / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008565:Membrane Proteins; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional / Q000276:immunology; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000502:physiology; D015398:Signal Transduction
D007370:Interferon Type I; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta