CD28 Deficiency Enhances Type I IFN Production by Murine Plasmacytoid Dendritic Cells.

Détails

ID Serval
serval:BIB_FE7AD6E7CB58
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
CD28 Deficiency Enhances Type I IFN Production by Murine Plasmacytoid Dendritic Cells.
Périodique
Journal of Immunology
Auteur(s)
Macal M., Tam M.A., Hesser C., Di Domizio J., Leger P., Gilliet M., Zuniga E.I.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
196
Numéro
4
Pages
1900-1909
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Type I IFNs (IFN-I) are key innate mediators that create a profound antiviral state and orchestrate the activation of almost all immune cells. Plasmacytoid dendritic cells (pDCs) are the most powerful IFN-I-producing cells and play important roles during viral infections, cancer, and autoimmune diseases. By comparing gene expression profiles of murine pDCs and conventional DCs, we found that CD28, a prototypic T cell stimulatory receptor, was highly expressed in pDCs. Strikingly, CD28 acted as a negative regulator of pDC IFN-I production upon TLR stimulation but did not affect pDC survival or maturation. Importantly, cell-intrinsic CD28 expression restrained pDC (and systemic) IFN-I production during in vivo RNA and DNA viral infections, limiting antiviral responses and enhancing viral growth early after exposure. Finally, CD28 also downregulated IFN-I response upon skin injury. Our study identified a new pDC regulatory mechanism by which the same CD28 molecule that promotes stimulation in most cells that express it is co-opted to negatively regulate pDC IFN-I production and limit innate responses.
Mots-clé
Animals, Antigens, CD28/immunology, Dendritic Cells/immunology, Dendritic Cells/metabolism, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Interferon Type I/biosynthesis, Interferon Type I/immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, Oligonucleotide Array Sequence Analysis, Real-Time Polymerase Chain Reaction, Transcriptome
Pubmed
Web of science
Open Access
Oui
Création de la notice
01/03/2016 17:34
Dernière modification de la notice
15/07/2020 5:22
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