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IL-17A attenuates IFN-λ expression by inducing suppressor of cytokine signaling expression in airway epithelium
http://hdl.handle.net/10271/00003665
http://hdl.handle.net/10271/000036653e5006d4-ba7c-4a12-9bc2-9a1d1def5a47
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
論文本文 (2.3 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2019-12-05 | |||||
| タイトル | ||||||
| タイトル | IL-17A attenuates IFN-λ expression by inducing suppressor of cytokine signaling expression in airway epithelium | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
| 資源タイプ | doctoral thesis | |||||
| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| その他のタイトル | ||||||
| その他のタイトル | 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 | |||||
| 言語 | ja | |||||
| 著者 |
丹羽, 充
× 丹羽, 充 |
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| 書誌情報 |
en : The Journal of Immunology 巻 201, 号 8, p. 2392-2402, 発行日 2018-10-15 |
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| 出版者 | ||||||
| 出版者 | American Association of Immunologists | |||||
| 言語 | en | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | 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. | |||||
| 言語 | en | |||||
| 学位名 | ||||||
| 言語 | ja | |||||
| 学位名 | 博士（医学） | |||||
| 学位の区分 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | doctoral | |||||
| 言語 | en | |||||
| 学位の分野 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 医学系研究科 | |||||
| 言語 | ja | |||||
| 学位授与機関 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 13820 | |||||
| 言語 | ja | |||||
| 学位授与機関名 | 浜松医科大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2019-03-13 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲第797号 | |||||
| ISSN | ||||||
| 収録物識別子タイプ | PISSN | |||||
| 収録物識別子 | 0022-1767 | |||||
| EISSN | ||||||
| 収録物識別子タイプ | EISSN | |||||
| 収録物識別子 | 1550-6606 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 30224514 | |||||
| 出版社DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.4049/jimmunol.1800147 | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
