IL-17A attenuates IFN-λ expression by inducing suppressor of cytokine signaling expression in airway epithelium 8

• Material Type: 博士論文
• ISSN: 0022-1767
• Title: IL-17A attenuates IFN-λ expression by inducing suppressor of cytokine signaling expression in airway epithelium
• Volume: 201 8
• Author/Editor: 丹羽, 充
• Author Heading: 丹羽, 充
• Publication, Distribution, etc.: American Association of Immunologists
• Publication Date: 2018-10-15
• Publication Date (W3CDTF): 2018-10-15
• 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
• Periodical title: The Journal of Immunology
• Degree grantor/type: 浜松医科大学
• Date Granted: 2019-03-13
• Date Granted (W3CDTF): 2019-03-13
• Dissertation Number: 甲第797号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第797号
• Text Language Code: eng
• Target Audience: 一般
• Note (General): doctoral; 医学系研究科; 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.
• DOI: info:doi/10.4049/jimmunol.1800147; https://doi.org/info:doi/10.4049/jimmunol.1800147
• Persistent ID (NDL): info:ndljp/pid/11429074; https://dl.ndl.go.jp/pid/11429074
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2020-01-15T13:48:52+09:00
• Date Created (W3CDTF): 2019-12-05
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10271/00003665; https://hama-med.repo.nii.ac.jp/records/3528
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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2023-12-06 再収集