Differential responsiveness to IFN-alpha and IFN-beta of human mature DC through modulation of IFNAR expression. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Leukocyte Biology Année : 2006

Differential responsiveness to IFN-alpha and IFN-beta of human mature DC through modulation of IFNAR expression.

Résumé

In human monocyte-derived dendritic cells (DC), infection with Mycobacterium tuberculosis and viruses or stimulation with Toll-like receptor type 3 and 4 agonists causes the release of type I interferon (IFN). Here, we describe that the IFN-beta released upon stimulation with lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly I:C) is responsible for a rapid and sustained signal transducer and activator of transcription 1 and 2 activation and expression of IFN-stimulated genes, such as the transcription factor IFN regulatory factor 7 and the chemokine CXC chemokine ligand 10. The autocrine production of IFN-beta from LPS and poly I:C-matured DC (mDC) induced a temporary saturation of the response to type I IFN and a marked decline in the level of the two IFN receptor (IFNAR) subunits. It is interesting that we found that upon clearing of the released cytokines, LPS-stimulated DC reacquired full responsiveness to IFN-beta but only partial responsiveness to IFN-alpha, and their maturation process was unaffected. Monitoring of surface and total levels of the receptor subunits showed that maximal expression of IFNAR2 resumed within 24 h of clearing, and IFNAR1 expression remained low. Thus, mDC can modulate their sensitivity to two IFN subtypes through a differential regulation of the IFNAR subunits.

Domaines

Immunologie
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Dates et versions

pasteur-00161981 , version 1 (12-07-2007)

Identifiants

Citer

M. Severa, M.E. Remoli, E. Giacomini, Josiane Ragimbeau, R. Lande, et al.. Differential responsiveness to IFN-alpha and IFN-beta of human mature DC through modulation of IFNAR expression.. Journal of Leukocyte Biology, 2006, 79(6), pp.1286-94. ⟨10.1189/jlb.1205742⟩. ⟨pasteur-00161981⟩
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