title: Control of pathogenic effector T-cell activities in situ by PD-L1 expression on respiratory inflammatory dendritic cells during respiratory syncytial virus infection.
abstract: Respiratory syncytial virus (RSV) infection is a leading cause of severe lower respiratory tract illness in young infants, the elderly and immunocompromised individuals. We demonstrate here that the co-inhibitory molecule programmed cell death 1 (PD-1) is selectively upregulated on T cells within the respiratory tract during both murine and human RSV infection. Importantly, the interaction of PD-1 with its ligand PD-L1 is vital to restrict the pro-inflammatory activities of lung effector T cells in situ, thereby inhibiting the development of excessive pulmonary inflammation and injury during RSV infection. We further identify that PD-L1 expression on lung inflammatory dendritic cells is critical to suppress inflammatory T-cell activities, and an interferon-STAT1-IRF1 axis is responsible for increased PD-L1 expression on lung inflammatory dendritic cells. Our findings suggest a potentially critical role of PD-L1 and PD-1 interactions in the lung for controlling host inflammatory responses and disease progression in clinical RSV infection.
authors.affiliation: Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: S
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: L
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: E K
authors.initials: EK
authors.lastname: Moser
authors.affiliation: Pediatric Pulmonology, Allergy and Sleep Medicine, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: L B
authors.initials: LB
authors.lastname: Jewett
authors.affiliation: Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wright
authors.affiliation: Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: J
authors.initials: J
authors.lastname: Du
authors.affiliation: 1] Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA [2] Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: B
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Pediatric Pulmonology, Allergy and Sleep Medicine, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Davis
authors.affiliation: Pediatric Pulmonology, Allergy and Sleep Medicine, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: Krupp
authors.affiliation: Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Braciale
authors.affiliation: 1] Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA [2] Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: J
authors.initials: J
authors.lastname: Sun
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism; D007372:Interferons / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
chemical_list: D060890:B7-H1 Antigen; D050856:Interferon Regulatory Factor-1; D061026:Programmed Cell Death 1 Receptor; D050794:STAT1 Transcription Factor; D007372:Interferons