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Elucidation of fibrosis in hypersensitivity pneumonitis: Antigen-presenting cells and gdT cells

Research Project

Project/Area Number 20K08515
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Miyazaki Yasunari  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30396999)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords過敏性肺炎 / 樹状細胞 / γδT細胞 / 線維化 / 抗原提示細胞
Outline of Research at the Start

慢性過敏性肺炎は潜在性に肺が線維化する。慢性・線維化するタイプは国内推定2万人の患者が存在し、5年生存率は30~40%と極めて予後不良である。申請者は慢性過敏性肺炎患者ではTH1/TH2バランスの変化あること見いだした。しかしその肺線維症発症のメカニズムは未だ不明である。本研究では本症の免疫反応の変化が肺線維化を誘導することを明らかにし、予後不良因子である線維化抑制治療に応用可能な研究を目指して① 抗原の種類による樹状細胞の役割② 急性・慢性期におけるgdT 細胞の役割③ 肺線維症関連の樹状細胞・gdT細胞群の同定 の3つの研究を行う。

Outline of Final Research Achievements

Hypersensitivity pneumonitis develops due to an allergic reaction caused by a chain of antigen-presenting cells and immune cells. In this study, we elucidated the roles of dendritic cells and γδT cells in fibrosis, which have not been elucidated in the chain process of allergic reactions. IL-17A-producing γδ T cells were found to increase in bird-associated hypersensitivity pneumonitis, but not in the farmer's lung model. ConventionalDC2 was predominantly increased in the anti-bird-associated hypersensitivity pneumonitis model, suggesting that it is related to immune linkage to Th17.

Academic Significance and Societal Importance of the Research Achievements

過敏性肺炎は特定の抗原に対する免疫・アレルギー反応で発症する間質性肺炎である。このうち慢性過敏性肺炎は潜在性に肺が線維化する。慢性・線維化するタイプはの5年生存率は30〜40%と極めて予後不良である。本研究成果により特発性肺線維症にも共通する肺線維化のメカニズムが明らかになり、線維化をきたす間質性肺炎の治療の一助になると考える。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (35 results)

All 2023 2022 2021 2020

All Journal Article (19 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 13 results,  Open Access: 3 results) Presentation (16 results) (of which Invited: 11 results)

  • [Journal Article] Database analysis of hypersensitivity pneumonitis in Japan2023

    • Author(s)
      Yamashita Shohei、Okamoto Tsukasa、Kawahara Tatsuo、Tateishi Tomoya、Anzai Tatsuhiko、Takahashi Kunihiko、Fushimi Kiyohide、Miyazaki Yasunari
    • Journal Title

      Respiratory Investigation

      Volume: 61 Issue: 2 Pages: 172-180

    • DOI

      10.1016/j.resinv.2022.12.003

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Understanding the process of people with hypersensitivity pneumonitis implementing continuous antigen avoidance and their affecting situations: A grounded theory study2022

    • Author(s)
      Kawamoto Yuko、Yatomi Yumiko、Furusawa Haruhiko、Hanzawa Satoshi、Miyazaki Yasunari、Tanaka Makoto
    • Journal Title

      Journal of Clinical Nursing

      Volume: 32 Issue: 11-12 Pages: 2880-2891

    • DOI

      10.1111/jocn.16395

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of serum surfactant protein-D as a prognostic predictor in fibrotic hypersensitivity pneumonitis.2022

    • Author(s)
      Ejima M, Okamoto T, Suzuki T, Miyazaki Y
    • Journal Title

      Respiratory investigation

      Volume: 60 Issue: 3 Pages: 369-378

    • DOI

      10.1016/j.resinv.2021.12.003

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Successful diagnosis of humidifier lung by individual provocation test to a responsible environment, a case report2022

    • Author(s)
      Murakami T、Iijima Y、Ando T、Ejima M、Shirai Tsuyoshi、Furusawa H、Okamoto T、Tateishi T、Tamaoka M、Miyazaki Y
    • Journal Title

      Respiratory Medicine Case Reports

      Volume: 37 Pages: 101639-101639

    • DOI

      10.1016/j.rmcr.2022.101639

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 【びまん性肺疾患における多職種合議(MDD)診断とAI支援の現在と未来】過敏性肺炎の診断アプローチ(2020ATS/JRS/ALAT過敏性肺炎ガイドライン、2021CHEST過敏性肺炎ガイドライン)とMDDについて2022

    • Author(s)
      宮崎 泰成, 惠島 將, 岡本 師
    • Journal Title

      呼吸器内科

      Volume: 41 Pages: 119-124

    • Related Report
      2021 Research-status Report
  • [Journal Article] 【呼吸器症候群(第3版)-その他の呼吸器疾患を含めて-】びまん性肺疾患 肉芽腫性肺疾患 肉芽腫性間質性肺炎2022

    • Author(s)
      宮崎泰成
    • Journal Title

      日本臨床

      Volume: 別冊 Pages: 123-126

    • Related Report
      2021 Research-status Report
  • [Journal Article] 臨床検査アップデート 鳥特異的IgG抗体 過敏性肺炎診断におけるイムノキャップ特異的IgG鳥測定の意義2021

    • Author(s)
      白井 剛, 宮崎 泰成
    • Journal Title

      Modern Media

      Volume: 67 Pages: 501-505

    • Related Report
      2021 Research-status Report
  • [Journal Article] 【間質性肺炎 徹底討論!-鳥からは逃げられない過敏性肺炎,放置してよいのかILA】慢性過敏性肺炎の診断と治療2021

    • Author(s)
      立石 知也, 惠島 将, 宮崎 泰成
    • Journal Title

      呼吸器ジャーナル

      Volume: 69 Pages: 403-412

    • Related Report
      2021 Research-status Report
  • [Journal Article] 慢性過敏性肺炎の遺伝子発現解析2021

    • Author(s)
      古澤 春彦, 宮崎 泰成
    • Journal Title

      呼吸器内科

      Volume: 40 Pages: 182-189

    • NAID

      40022670064

    • Related Report
      2021 Research-status Report
  • [Journal Article] 【過敏性肺炎ガイドラインを読み解く】抗原回避試験2021

    • Author(s)
      筒井 俊晴, 宮崎 泰成
    • Journal Title

      呼吸器内科

      Volume: 40 Pages: 164-169

    • Related Report
      2021 Research-status Report
  • [Journal Article] Alternative gene expression by TOLLIP variant is associated with lung function in chronic hypersensitivity pneumonitis.2021

    • Author(s)
      Katayanagi S, Setoguchi Y, Kitagawa S, Okamoto T, Miyazaki Y
    • Journal Title

      Chest

      Volume: 161 Issue: 2 Pages: 458-469

    • DOI

      10.1016/j.chest.2021.08.052

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Efficacy of treatment with corticosteroids for fibrotic hypersensitivity pneumonitis: a propensity score-matched cohort analysis2021

    • Author(s)
      Ejima Masaru, Okamoto Tsukasa, Suzuki Takafumi, Anzai Tatsuhiko, Takahashi Kunihiko, Miyazaki Yasunari
    • Journal Title

      BMC PULMONARY MEDICINE

      Volume: 21 Issue: 1 Pages: 243-243

    • DOI

      10.1186/s12890-021-01608-1

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Screening and diagnosis of acute and chronic bird-related hypersensitivity pneumonitis by serum IgG and IgA antibodies to bird antigens with ImmunoCAP®2021

    • Author(s)
      Shirai T, Tanino Y, Nikaido T, Takaku Y, Hashimoto S, Taguchi Y, Baba T, Ogura T, Kataoka K, Nakayama M, Yamada Y, Matsushima S, Nakayama S, Miyazaki Y
    • Journal Title

      Allergology International

      Volume: 70 Issue: 2 Pages: 208-214

    • DOI

      10.1016/j.alit.2020.09.003

    • NAID

      130008024347

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] IL-17A-Secreting Memory γδ T Cells Play a Pivotal Role in Sensitization and Development of Hypersensitivity Pneumonitis.2021

    • Author(s)
      Takashi Yamana, Tsukasa Okamoto, Masahiro Ishizuka, Satoshi Hanzawa, Masaru Ejima, Sho Shibata, Yasunari Miyazaki
    • Journal Title

      Journal of immunology

      Volume: 206 Issue: 2 Pages: 355-365

    • DOI

      10.4049/jimmunol.2000198

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exposure Assessment Tools for Hypersensitivity Pneumonitis. An Official American Thoracic Society Workshop Report.2020

    • Author(s)
      Kerri A Johannson, Hayley Barnes, Anne-Pauline Bellanger, et al.
    • Journal Title

      Annals of the American Thoracic Society

      Volume: 17 Issue: 12 Pages: 1501-1509

    • DOI

      10.1513/annalsats.202008-942st

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Disruption in the balance between apolipoprotein A-I and mast cell chymase in chronic hypersensitivity pneumonitis.2020

    • Author(s)
      Yukihisa Inoue, Tsukasa Okamoto, Takayuki Honda, Yoshihisa Nukui, Takumi Akashi, Tamiko Takemura, Minoru Tozuka, Yasunari Miyazaki
    • Journal Title

      Immunity, inflammation and disease

      Volume: 8 Issue: 4 Pages: 659-671

    • DOI

      10.1002/iid3.355

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hypersensitivity pneumonitis.2020

    • Author(s)
      Ulrich Costabel, Yasunari Miyazaki, Annie Pardo, Dirk Koschel, Francesco Bonella, Paolo Spagnolo, Josune Guzman, Christopher J Ryerson, Moises Selman
    • Journal Title

      Nature reviews. Disease primers

      Volume: 6 Issue: 1 Pages: 65-65

    • DOI

      10.1038/s41572-020-0191-z

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Changes in serum KL-6 levels during short-term strict antigen avoidance are associated with the prognosis of patients with fibrotic hypersensitivity pneumonitis caused by avian antigens2020

    • Author(s)
      Hanzawa Satoshi、Tateishi Tomoya、Ishizuka Masahiro、Inoue Yukihisa、Honda Takayuki、Kawahara Tatsuo、Tomita Makoto、Miyazaki Yasunari
    • Journal Title

      Respiratory Investigation

      Volume: 58 Issue: 6 Pages: 457-464

    • DOI

      10.1016/j.resinv.2020.05.007

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] High-resolution CT features distinguishing usual interstitial pneumonia pattern in chronic hypersensitivity pneumonitis from those with idiopathic pulmonary fibrosis2020

    • Author(s)
      Tateishi Tomoya、Johkoh Takeshi、Sakai Fumikazu、Miyazaki Yasunari、Ogura Takashi、Ichikado Kazuya、Suda Takafumi、Taguchi Yoshio、Inoue Yoshikazu、Takemura Tamiko、Colby Thomas V.、Sumikawa Hiromitsu、Fujimoto Kiminori、Arakawa Hiroaki、Raoof Suhail、Inase Naohiko
    • Journal Title

      Japanese Journal of Radiology

      Volume: 38 Issue: 6 Pages: 524-532

    • DOI

      10.1007/s11604-020-00932-6

    • NAID

      50014524561

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] 過敏性肺炎の診断・治療(アドバンス)2023

    • Author(s)
      宮崎泰成
    • Organizer
      第9回総合アレルギー講習会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] アレルギー性肺疾患(類縁疾患)の基本から最新情報まで 過敏性肺炎2022

    • Author(s)
      宮崎泰成
    • Organizer
      第8回総合アレルギー講習会
    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Invited
  • [Presentation] 過敏性肺炎 原因抗原の特定2022

    • Author(s)
      宮崎泰成
    • Organizer
      日本アレルギー学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] シンポジウム びまん 性肺疾患の最近のステートメント・手引きを議論する2022

    • Author(s)
      宮崎泰成
    • Organizer
      第62回日本呼吸器学会学術講演会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 教育講演3 過敏性肺炎2021

    • Author(s)
      宮崎泰成
    • Organizer
      第6回日本アレルギー学会関東地方会 日本アレルギー学会関東地方会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 教育講演1 過敏性肺炎をめぐる最近の話題2021

    • Author(s)
      宮崎泰成
    • Organizer
      第41回日本サルコイドーシス ・肉芽腫性疾患学会総
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] シンポジウム7 生活環境汚染とアレルギー 生活環境汚染と肺疾患2021

    • Author(s)
      宮崎泰成
    • Organizer
      日本アレルギー学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 敏性肺炎国際ガイドラインの問題点と展望 ACCPガイドラインとの整合性2021

    • Author(s)
      宮崎泰成
    • Organizer
      日本呼吸器学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 過敏性肺炎の診断アップデート 原因抗原の特定2021

    • Author(s)
      宮崎泰成
    • Organizer
      日本呼吸器学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 慢性過敏性肺炎の診断と治療2021

    • Author(s)
      宮崎泰成
    • Organizer
      日本呼吸器学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] DPC病名を用いた日本における過敏性肺炎の疫学的研究2020

    • Author(s)
      山下 将平, 岡本 師, 本多 隆行, 白井 剛, 石塚 聖洋, 立石 知也, 伏見 清秀, 宮崎 泰成
    • Organizer
      日本呼吸器学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 左右差のある慢性過敏性肺炎の臨床的特徴2020

    • Author(s)
      高澤 聖子, 岡本 師, 三ツ村 隆弘, 須原 宏造, 本多 隆行, 白井 剛, 石塚 聖洋, 立石 知也, 宮崎 泰成
    • Organizer
      日本呼吸器学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 慢性過敏性肺炎に対する抗線維化薬使用例の検討2020

    • Author(s)
      飯島 裕基, 榊原 里江, 本多 隆行, 三ツ村 隆弘, 白井 剛, 石塚 聖洋, 岡本 師, 立石 知也, 玉岡 明洋, 宮崎 泰成
    • Organizer
      日本呼吸器学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 本邦の慢性過敏性肺炎におけるMUC5Bプロモーター多型の解析2020

    • Author(s)
      片柳 真司, 岡本 師, 瀬戸口 靖弘, 宮崎 泰成
    • Organizer
      日本呼吸器学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 吸入誘発試験を施行した加湿器肺6例の検討2020

    • Author(s)
      河原 達雄, 飯島 裕基, 本多 隆行, 白井 剛, 石塚 聖洋, 岡本 師, 立石 知也, 玉岡 明洋, 宮崎 泰成
    • Organizer
      日本呼吸器学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 慢性過敏性肺炎における進行性線維化フェノタイプ2020

    • Author(s)
      宮崎泰成
    • Organizer
      日本呼吸器学会
    • Related Report
      2020 Research-status Report
    • Invited

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Published: 2020-04-28   Modified: 2024-01-30  

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