title: Plasmacytoid Dendritic Cells Die by the CD8 T Cell-Dependent Perforin Pathway during Acute Nonviral Inflammation.
abstract: Regulation of the inflammatory response involves the control of dendritic cell survival. To our knowledge, nothing is known about the survival of plasmacytoid dendritic cells (pDC) in such situation. pDC are specialized in type I IFN (IFN-I) secretion to control viral infections, and IFN-I also negatively regulate pDC survival during the course of viral infections. In this study, we asked about pDC behavior in the setting of virus-free inflammation. We report that pDC survival was profoundly reduced during different nonviral inflammatory situations in the mouse, through a mechanism independent of IFN-I and TLR signaling. Indeed, we demonstrated that during inflammation, CD8(+) T cells induced pDC apoptosis through the perforin pathway. The data suggest, therefore, that pDC have to be turned down during ongoing acute inflammation to not initiate autoimmunity. Manipulating CD8(+) T cell response may therefore represent a new therapeutic opportunity for the treatment of pDC-associated autoimmune diseases, such as lupus or psoriasis.
authors.affiliation: INSERM, UMR1098, F-25000 Besançon, France; Université Bourgogne Franche-Comté, UMR1098, F-25000 Besançon, France; Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, F-25000 Besançon, France; and LabEx LipSTIC, ANR-11-LABX-0021, FHU INCREASE, F-25000 Besançon, France.
authors.forename: Adrien
authors.identifier: 0000-0001-5986-2762
authors.initials: A
authors.lastname: Mossu
authors.affiliation: INSERM, UMR1098, F-25000 Besançon, France; Université Bourgogne Franche-Comté, UMR1098, F-25000 Besançon, France; Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, F-25000 Besançon, France; and LabEx LipSTIC, ANR-11-LABX-0021, FHU INCREASE, F-25000 Besançon, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Daoui
authors.affiliation: INSERM, UMR1098, F-25000 Besançon, France; Université Bourgogne Franche-Comté, UMR1098, F-25000 Besançon, France; Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, F-25000 Besançon, France; and LabEx LipSTIC, ANR-11-LABX-0021, FHU INCREASE, F-25000 Besançon, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Bonnefoy
authors.affiliation: INSERM, UMR1098, F-25000 Besançon, France; Université Bourgogne Franche-Comté, UMR1098, F-25000 Besançon, France; Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, F-25000 Besançon, France; and LabEx LipSTIC, ANR-11-LABX-0021, FHU INCREASE, F-25000 Besançon, France.
authors.forename: Lucie
authors.identifier: 0000-0002-3459-7904
authors.initials: L
authors.lastname: Aubergeon
authors.affiliation: INSERM, UMR1098, F-25000 Besançon, France; Université Bourgogne Franche-Comté, UMR1098, F-25000 Besançon, France; Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, F-25000 Besançon, France; and LabEx LipSTIC, ANR-11-LABX-0021, FHU INCREASE, F-25000 Besançon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Saas
authors.affiliation: INSERM, UMR1098, F-25000 Besançon, France; Université Bourgogne Franche-Comté, UMR1098, F-25000 Besançon, France; Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, F-25000 Besançon, France; and LabEx LipSTIC, ANR-11-LABX-0021, FHU INCREASE, F-25000 Besançon, France sylvain.perruche@inserm.fr.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Perruche
mesh_terms: D000818:Animals; D017209:Apoptosis; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002470:Cell Survival; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000473:pathology*; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism; D051379:Mice; D054353:Perforin / Q000276:immunology / Q000378:metabolism*; D051199:Toll-Like Receptor 7 / Q000378:metabolism
chemical_list: D016207:Cytokines; D016898:Interferon-alpha; D051199:Toll-Like Receptor 7; D054353:Perforin