title: Loss of type I IFN receptors and impaired IFN responsiveness during terminal maturation of monocyte-derived human dendritic cells.
abstract: 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.
authors.affiliation: Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Gauzzi
authors.forename: Irene
authors.initials: I
authors.lastname: Canini
authors.forename: Pierre
authors.initials: P
authors.lastname: Eid
authors.forename: Filippo
authors.initials: F
authors.lastname: Belardelli
authors.forename: Sandra
authors.initials: S
authors.lastname: Gessani
mesh_terms: 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
chemical_list: D007370:Interferon Type I; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta