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長時間作用性ムスカリン受容体拮抗薬は2型自然リンパ球を介する好酸球性気道炎症を制御する
http://hdl.handle.net/10232/00031786
http://hdl.handle.net/10232/0003178621fa67a3-45e0-42da-982d-1588310b683f
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Diss_松山_崇弘_ISK619_2021 (4.4 MB)
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Abstract_松山_崇弘_4515810161_2021 (26.7 kB)
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Result_Matsuyama_Takahiro_isk_619 (229.4 kB)
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Comments_Matsuyama_Takahiro_isk_619 (107.7 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-10-06 | |||||
| タイトル | ||||||
| タイトル | Long-acting muscarinic antagonist regulates group 2 innate lymphoid cell-dependent airway eosinophilic inflammation | |||||
| タイトル言語 | en | |||||
| タイトル | ||||||
| タイトル | 長時間作用性ムスカリン受容体拮抗薬は2型自然リンパ球を介する好酸球性気道炎症を制御する | |||||
| タイトル言語 | ja | |||||
| 著者 |
松山, 崇弘
× 松山, 崇弘 |
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| 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 | |||||
| 要約 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Background: Tiotropium bromide, a long-acting muscarinic antagonist, reduces the frequency of exacerbation in patients with moderate to severe asthma, but its underlying mechanism is not clear. Asthma exacerbations are associated with exposure to external stimuli, and group 2 innate lymphoid cells (ILC2s) are considered to be involved in the pathophysiology of asthma exacerbation. We investigated whether tiotropium modulates airway inflammation through ILC2 functions. Methods: Mice were administered papain intranasally to induce innate-type airway inflammation with or without tiotropium pretreatment, and bronchoalveolar lavage fluids (BALF) and lung tissues were collected. Lung-derived ILC2s and bone marrow-derived basophils were stimulated in vitro with IL-33 in the presence or absence of tiotropium. Muscarinic M3 receptor (M3R) expression on immune cells was assessed by RNA sequence. Results: Papain induced airway eosinophilic inflammation, and tiotropium reduced the numbers of eosinophils in BALF. The concentrations of IL-4, IL-5, and IL-13, and the numbers of ILC2s in BALF were also reduced by tiotropium treatment. However, tiotropium did not affect IL-33-induced IL-5 and IL-13 production from ILC2s, suggesting that tiotropium regulates ILC2s indirectly. Gene-expression analysis showed that basophils predominantly expressed M3R mRNA among murine immune cells. Tiotropium reduced IL-4 production from basophils derived from mouse bone marrow and human basophils after stimulation with IL-33. Conclusions: These findings suggest that tiotropium attenuates ILC2-dependent airway inflammation by suppressing IL-4 production from basophils and, subsequently, regulating ILC2 activation. The inhibitory effects of long-acting muscarinic antagonists on the innate response may contribute to reducing asthma exacerbation. This is the peer reviewed version of the following article: Takahiro Matsuyama, Kentaro Machida, Yasutaka Motomura, Koichi Takagi, Yoichi Doutake, Asako Tanoue-Hamu, Kiyotaka Kondo, Keiko Mizuno, Kazuyo Moro, Hiromasa Inoue Long-acting muscarinic antagonist regulates group 2 innate lymphoid cell-dependent airway eosinophilic inflammation Allergy (2021), 76(9), 2785–2796 © 2021 EAACI and John Wiley and Sons A/S. which has been published in final form at https://doi.org/10.1111/all.14836 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. |
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| 内容記述言語 | en | |||||
| 作成日 | ||||||
| 日付 | 2021-09-03 | |||||
| 日付タイプ | Collected | |||||
| 出版タイプ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| NDC | ||||||
| 主題Scheme | NDC | |||||
| 主題 | 490 | |||||
| ファイル（説明） | ||||||
| 内容記述 | 博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨 | |||||
| 公開者・出版者 | ||||||
| 出版者 | John Wiley and Sons Ltd | |||||
| 出版者言語 | en | |||||
| 公開者・出版者 | ||||||
| 出版者 | 鹿児島大学 | |||||
| 出版者言語 | ja | |||||
| 備考 | ||||||
| 備考言語 | ja | |||||
| 備考 | 【指導教員:井上博雅】 | |||||
| date.appl | ||||||
| appl | 【学位申請日】2021-04-07 | |||||
| 学位名 | ||||||
| 学位名の言語 | ja | |||||
| 学位名 | 博士(医学) | |||||
| 学位名 | ||||||
| 学位名の言語 | en | |||||
| 学位名 | Doctor of Philosophy in Medical Science | |||||
| 学位授与機関名 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 17701 | |||||
| 学位授与機関名の言語 | ja | |||||
| 学位授与機関名 | 鹿児島大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2021-09-14 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲総研第619号 | |||||
