Loss of type I IFN receptors and impaired IFN responsiveness during terminal maturation of monocyte-derived human dendritic cells.
J Immunol
; 169(6): 3038-45, 2002 Sep 15.
Article
en En
| MEDLINE
| ID: mdl-12218119
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Interferón Tipo I
/
Regulación hacia Abajo
/
Receptores de Interferón
Límite:
Humans
Idioma:
En
Revista:
J Immunol
Año:
2002
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Estados Unidos