title: IL-17E (IL-25) and IL-17RB promote respiratory syncytial virus-induced pulmonary disease.
abstract: One of the most severe pathologic responses of RSV infection is associated with overproduction of cytokines and inflammation, leading to mucus hypersecretion. This study investigated the role of IL-25 in the development of RSV-associated immunopathology. IL-25 and its receptor IL-17RB were increased following RSV infection, and IL-25 blockade using neutralizing antibodies reduced RSV-associated pathology, AHR, and type 2 cytokine production. Likewise, IL-17RB-/-mice demonstrated a modified inflammatory response during RSV infection characterized by decreased Th2 and increased Th17 cytokine production. Additionally, the IL-17RB-/-mice demonstrated significantly reduced inflammation and cytokine production in a model of RSV-driven asthma exacerbation. These results indicate that IL-25 regulates the inflammatory response to RSV infection and that its inhibition may enable a reduction in the severity of RSV-associated pulmonary inflammation, including during viral-induced asthma exacerbation.
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Petersen
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Vladislav
authors.initials: V
authors.lastname: Dolgachev
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Rasky
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA nlukacs@umich.edu.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Lukacs
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000821:virology; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology
chemical_list: C485810:Il17rb protein, mouse; D007378:Interleukins; C442281:Mydgf protein, mouse; D053722:Receptors, Interleukin-17
keywords: Th2; cytokines; mucus