title: IL-4Rα on CD4+ T cells plays a pathogenic role in respiratory syncytial virus reinfection in mice infected initially as neonates.
abstract: RSV is the major cause of severe bronchiolitis in infants, and severe bronchiolitis as a result of RSV is associated with subsequent asthma development. A biased Th2 immune response is thought to be responsible for neonatal RSV pathogenesis; however, molecular mechanisms remain elusive. Our data demonstrate, for the first time, that IL-4Rα is up-regulated in vitro on human CD4(+) T cells from cord blood following RSV stimulation and in vivo on mouse pulmonary CD4(+) T cells upon reinfection of mice, initially infected as neonates. Th cell-specific deletion of Il4ra attenuated Th2 responses and abolished the immunopathophysiology upon reinfection, including airway hyper-reactivity, eosinophilia, and mucus hyperproduction in mice infected initially as neonates. These findings support a pathogenic role for IL-4Rα on Th cells following RSV reinfection of mice initially infected as neonates; more importantly, our data from human cells suggest that the same mechanism occurs in humans.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Dahui
authors.initials: D
authors.lastname: You
authors.forename: Nico
authors.initials: N
authors.lastname: Marr
authors.forename: Jordy
authors.initials: J
authors.lastname: Saravia
authors.forename: Bishwas
authors.initials: B
authors.lastname: Shrestha
authors.forename: Greg I
authors.initials: GI
authors.lastname: Lee
authors.forename: Stuart E
authors.initials: SE
authors.lastname: Turvey
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
authors.forename: De'Broski R
authors.initials: DR
authors.lastname: Herbert
authors.forename: Stephania A
authors.initials: SA
authors.lastname: Cormier
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D053662:Interleukin-4 Receptor alpha Subunit / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D053662:Interleukin-4 Receptor alpha Subunit
keywords: T helper cells; infants; viral infection
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