Details

Autor(en) / Beteiligte

• Gauzzi, Maria Cristina
• Canini, Irene
• Eid, Pierre
• Belardelli, Filippo
• Gessani, Sandra

Titel

Loss of Type I IFN Receptors and Impaired IFN Responsiveness During Terminal Maturation of Monocyte-Derived Human Dendritic Cells

Ist Teil von

• The Journal of immunology (1950), 2002-09, Vol.169 (6), p.3038-3045

Ort / Verlag

United States: Am Assoc Immnol

Erscheinungsjahr

2002

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.