title: Type I IFN signaling facilitates the development of IL-10-producing effector CD8+T cells during murine influenza virus infection.
abstract: Recent evidence has suggested that IL-10-producing effector CD8+T cells play an important role in regulating excessive inflammation during acute viral infections. However, the cellular and molecular cues regulating the development of IL-10-producing effector CD8+T cells are not completely defined. Here, we show that type I interferons (IFNs) are required for the development of IL-10-producing effector CD8+T cells during influenza virus infection in mice. We find that type I IFNs can enhance IL-27 production by lung APCs, thereby facilitating IL-10-producing CD8+T-cell development through a CD8+T-cell-nonautonomous way. Surprisingly, we also demonstrate that direct type I IFN signaling in CD8+T cells is required for the maximal generation of IL-10-producing CD8+T cells. Type I IFN signaling in CD8+T cells, in cooperation with IL-27 and IL-2 signaling, promotes and sustains the expression of IFN regulatory factor 4 (IRF4) and B-lymphocyte-induced maturation protein-1 (Blimp-1), two transcription factors required for the production of IL-10 by effector CD8+T cells. Our data reveal a critical role of the innate antiviral effector cytokines in regulating the production of a regulatory cytokine by effector CD8+T cells during respiratory virus infection.
authors.affiliation: Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.|Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.|Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.|Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Su
authors.initials: S
authors.lastname: Huang
authors.affiliation: Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wright
authors.affiliation: Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Braciale
authors.affiliation: Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.|Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007251:Influenza, Human / Q000276:immunology*; D007370:Interferon Type I / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008168:Lung / Q000473:pathology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009975:Orthomyxoviridae / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D053633:Receptor, Interferon alpha-beta / Q000235:genetics; D050795:STAT2 Transcription Factor / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C508032:Ifnar1 protein, mouse; D007370:Interferon Type I; D050795:STAT2 Transcription Factor; C494085:Stat2 protein, mouse; D016753:Interleukin-10; D053633:Receptor, Interferon alpha-beta
keywords: CD8+ T cells; IL-10; IL-27; Influenza; Type I IFN