title: Rhinovirus inhibits IL-17A and the downstream immune responses in allergic asthma.
abstract: The proinflammatory cytokine interleukin-17A (IL-17A) is known to mediate antimicrobial activity, but its role during rhinovirus (RV) infections and in asthma needs further investigation. Therefore, we addressed the role of IL-17A during allergic asthma and antiviral immune response in human and murine immunocompetent cells. In this study we found that asthmatic children with a RV infection in their upper airways have upregulated mRNA levels of the antiviral cytokine interferon type I (IFN)-β and the transcription factor T-box 21 (TBX21) and reduced levels of IL-17A protein in their peripheral blood mononuclear cells (PBMCs). We also found that IL-17A inhibited RV1b replication in infected human lung epithelial cells A549. Furthermore, by using gene array analysis we discovered that targeted deletion of Il17a in murine lung CD4(+) T cells impaired Oas1g mRNA downstream of Ifnβ, independently from RV infection. Additionally, in PBMCs of children with a RV infection in their nasalpharyngeal fluid OAS1 gene expression was found downregulated. Finally RV1b inhibited IL-17A production in lung CD4(+) T cells in a setting of experimental asthma. These results indicate that the RV1b inhibits IL-17A in T helper type 17 cells and IL-17A clears RV1b infection in epithelial cells. In both cases IL-17A contributes to fend off RV1b infection by inducing genes downstream of interferon type I pathway.
authors.affiliation: Department of Molecular Pneumology, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Graser
authors.affiliation: Institute of Humangenetics, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: A B
authors.initials: AB
authors.lastname: Ekici
authors.affiliation: Department of Molecular Pneumology, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Sopel
authors.affiliation: Paediatric Pneumology-Allergology, Department of Paediatrics and Adolescent Medicine, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: V O
authors.initials: VO
authors.lastname: Melichar
authors.affiliation: Paediatric Pneumology-Allergology, Department of Paediatrics and Adolescent Medicine, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Zimmermann
authors.affiliation: Allergy and Clinical Immunology Unit, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: N G
authors.initials: NG
authors.lastname: Papadopoulos
authors.affiliation: Allergy and Clinical Immunology Unit, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: S
authors.initials: S
authors.lastname: Taka
authors.affiliation: Institute of Humangenetics, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Ferrazzi
authors.affiliation: Department of Virology, University of Turku, Turku, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Vuorinen
authors.affiliation: Department of Molecular Pneumology, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Finotto
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000276:immunology; D000072283:A549 Cells; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002648:Child; D002675:Child, Preschool; D004342:Drug Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000821:virology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000821:virology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage; D010850:Picornaviridae Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D012229:Rhinovirus / Q000254:growth & development / Q000276:immunology*; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D016899:Interferon-beta; D010047:Ovalbumin; C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase