title: Autocrine regulation of pulmonary inflammation by effector T-cell derived IL-10 during infection with respiratory syncytial virus.
abstract: Respiratory syncytial virus (RSV) infection is the leading viral cause of severe lower respiratory tract illness in young infants. Clinical studies have documented that certain polymorphisms in the gene encoding the regulatory cytokine IL-10 are associated with the development of severe bronchiolitis in RSV infected infants. Here, we examined the role of IL-10 in a murine model of primary RSV infection and found that high levels of IL-10 are produced in the respiratory tract by anti-viral effector T cells at the onset of the adaptive immune response. We demonstrated that the function of the effector T cell -derived IL-10 in vivo is to limit the excess pulmonary inflammation and thereby to maintain critical lung function. We further identify a novel mechanism by which effector T cell-derived IL-10 controls excess inflammation by feedback inhibition through engagement of the IL-10 receptor on the antiviral effector T cells. Our findings suggest a potentially critical role of effector T cell-derived IL-10 in controlling disease severity in clinical RSV infection.
authors.affiliation: The Beirne B. Carter Center for Immunology Research, The University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.forename: Amber
authors.initials: A
authors.lastname: Cardani
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Sharma
authors.forename: Victor E
authors.initials: VE
authors.lastname: Laubach
authors.forename: Robert S
authors.initials: RS
authors.lastname: Jack
authors.forename: Werner
authors.initials: W
authors.lastname: Müller
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Braciale
mesh_terms: D000818:Animals; D001990:Bronchiolitis, Viral / Q000235:genetics / Q000276:immunology* / Q000821:virology; D004195:Disease Models, Animal; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D007223:Infant; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D053701:Receptors, Interleukin-10 / Q000235:genetics / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C556062:IL10 protein, mouse; D053701:Receptors, Interleukin-10; D016753:Interleukin-10