{"created":"2023-06-20T15:49:00.307093+00:00","id":3528,"links":{},"metadata":{"_buckets":{"deposit":"4e711d79-39f5-4281-b1fa-4cfec1209168"},"_deposit":{"created_by":4,"id":"3528","owners":[4],"pid":{"revision_id":0,"type":"depid","value":"3528"},"status":"published"},"_oai":{"id":"oai:hama-med.repo.nii.ac.jp:00003528","sets":["2:15:17"]},"author_link":["10363"],"control_number":"3528","item_5_alternative_title_1":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"気道上皮においてIL-17Aはサイトカインシグナル抑制因子発現の誘導を介してIFN-λ発現を減弱する","subitem_alternative_title_language":"ja"}]},"item_5_biblio_info_5":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2018-10-15","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"8","bibliographicPageEnd":"2402","bibliographicPageStart":"2392","bibliographicVolumeNumber":"201","bibliographic_titles":[{"bibliographic_title":"The Journal of Immunology","bibliographic_titleLang":"en"}]}]},"item_5_date_granted_17":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2019-03-13"}]},"item_5_degree_grantor_15":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"浜松医科大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"13820","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_5_degree_name_12":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(医学)","subitem_degreename_language":"ja"}]},"item_5_description_13":{"attribute_name":"学位の区分","attribute_value_mlt":[{"subitem_description":"doctoral","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_5_description_14":{"attribute_name":"学位の分野","attribute_value_mlt":[{"subitem_description":"医学系研究科","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_5_description_9":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"IFN-λ is a cytokine expressed in epithelial tissues and plays a central role in antiviral mucosal immune response. The expression of IFN-λ in the airway is impaired in chronic airway diseases (e.g., asthma, chronic obstructive pulmonary disease), which renders patients susceptible to viral infection. IL-17A is associated with asthma and chronic obstructive pulmonary disease pathogenesis; however, IL-17A regulation of IFN-λ expression remains unclear. The aim of the current study is to clarify IL-17A-mediated regulatory mechanisms of IFN-λ expression in human airway epithelial cells. In this study, we have shown that polyinosinic: polycytidylic acid (polyI:C) and influenza A virus (IAV) infection increased IFN-λ expression at mRNA and protein levels in primary cultures of normal human bronchial epithelial cells, whereas IL-17A attenuated polyI:C- or IAV-induced IFN-λ expression. IFN-λ receptor 1 knockdown and a JAK inhibitor, ruxolitinib, attenuated polyI:C-induced IFN-λ expression, confirming that a positive autocrine feedback loop, the IFN-λ receptor-JAK-STAT pathway, was involved in IFN-λ expression. In Western blotting analysis, we demonstrated that polyI:C and IAV infection induced STAT1 phosphorylation in normal human bronchial epithelial cells, whereas IL-17A suppressed polyI:C- or IAV-mediated STAT1 phosphorylation. Furthermore, we found that cotreatment with IL-17A and polyI:C or IAV infection synergistically increased suppressor of cytokine signaling (SOCS)1 and SOCS3 expression. SOCS1 small interfering RNA and SOCS3 small interfering RNA negated the inhibitory effect of IL-17A in polyI:C-induced IFN-λ expression by restoring attenuated STAT1 phosphorylation. Taken together, these findings indicate that IL-17A attenuates virus-induced IFN-λ expression by enhancing SOCS1 and SOCS3 expression to inhibit autocrine signaling loops in human airway epithelial cells.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_5_dissertation_number_18":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第797号"}]},"item_5_publisher_6":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"American Association of Immunologists","subitem_publisher_language":"en"}]},"item_5_relation_26":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"30224514","subitem_relation_type_select":"PMID"}}]},"item_5_relation_28":{"attribute_name":"出版社DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.4049/jimmunol.1800147","subitem_relation_type_select":"DOI"}}]},"item_5_source_id_19":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0022-1767","subitem_source_identifier_type":"PISSN"}]},"item_5_source_id_20":{"attribute_name":"EISSN","attribute_value_mlt":[{"subitem_source_identifier":"1550-6606","subitem_source_identifier_type":"EISSN"}]},"item_5_version_type_32":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"丹羽, 充","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"10363","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2019-12-05"}],"displaytype":"detail","filename":"DT_797ronbun.pdf","filesize":[{"value":"2.3 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"論文本文","objectType":"fulltext","url":"https://hama-med.repo.nii.ac.jp/record/3528/files/DT_797ronbun.pdf"},"version_id":"89a97813-a619-4ff2-a566-e719bdc93561"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"IL-17A attenuates IFN-λ expression by inducing suppressor of cytokine signaling expression in airway epithelium","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"IL-17A attenuates IFN-λ expression by inducing suppressor of cytokine signaling expression in airway epithelium","subitem_title_language":"en"}]},"item_type_id":"5","owner":"4","path":["17"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2019-12-05"},"publish_date":"2019-12-05","publish_status":"0","recid":"3528","relation_version_is_last":true,"title":["IL-17A attenuates IFN-λ expression by inducing suppressor of cytokine signaling expression in airway epithelium"],"weko_creator_id":"4","weko_shared_id":-1},"updated":"2023-10-16T08:00:07.386988+00:00"}