Differential responsiveness to IFN-α and IFN-β of human mature DC through modulation of IFNAR expression

Journal of Leukocyte Biology

Elena Giacomini³  Gilles Uzé¹  Roberto Lande³  Maria Elena Remoli³  Sandra Pellegrini²  Martina Severa³  Eliana M. Coccia³  Josiane Ragimbeau² 

[1] CNRS UMR 5124, Montpellier, France; and CNRS UMR 5124, Montpellier, France; and CNRS UMR 5124, Montpellier, France; and;Unit of Cytokine Signaling, CNRS URA 1961, Institut Pasteur, Paris, France Unit of Cytokine Signaling, CNRS URA 1961, Institut Pasteur, Paris, France Unit of Cytokine Signaling, CNRS URA 1961, Institut Pasteur, Paris, FranceDepartment of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy; Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy; Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy;

关键词: type I IFN;    cytokine receptor;    TLR;    LPS;   

DOI  :  10.1189/jlb.1205742

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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-β 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-β 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-β but only partial responsiveness to IFN-α, 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.

【 授权许可】

Unknown