Role of chemokines and prostanoids in fibrogenesis of hypersensitivity pneumonitis

• Project/Area Number: 16K09576
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Yasunari Miyazaki 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30396999)
• Research Collaborator: INOUE Yukihisa ; NUKUI Yoshihisa
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 肺線維化 / 過敏性肺炎 / ケモカイン / プロスタノイド / 肺繊維化

Outline of Final Research Achievements

We investigated mediators such as chemokines and cytokines using clinical samples to elucidate the fibrotic mechanism of chronic hypersensitivity pneumonia. It has been clarified that the neutrophil response / Th1 response seen in the acute phase of hypersensitivity pneumonitis during antigen inhalation even in the chronic phase (fibrosis phase) of hypersensitivity pneumonitis, and the extracellular organ protein related to Th2 cytokine, periostin, was found to be a marker of fibrosis and prognosis in patients with chronic hypersensitivity pneumonitis.

Academic Significance and Societal Importance of the Research Achievements

これらの研究成果は慢性過敏性肺炎の線維化機序を明らかにする初めての知見であり、平均生存期間が4～9年と短く、既存のステロイド治療の効果が少ない慢性線維化性過敏性肺炎において新しい治療を開発する一助になると考えられる。

Research Products

• [Journal Article] The Analysis of Surgical Lung Biopsy and Explanted Lung Specimens Sheds Light on the Pathological Progression of Chronic Bird-related Hypersensitivity Pneumonitis (2019)
  • Author(s): Hanzawa Satoshi、Tateishi Tomoya、Takemura Tamiko、Okada Yoshinori、Yamada Yoshihito、Noda Masafumi、Miyazaki Yasunari、Inase Naohiko
  • Journal Title: Internal Medicine Volume: 58 Issue: 8 Pages: 1145-1150
  • DOI: 10.2169/internalmedicine.1142-18
  • NAID: 130007632762
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2019-04-15
  • Peer Reviewed
• [Journal Article] Resequencing Study Confirms Host Defense and Cell Senescence Gene Variants Contribute to the Risk of Idiopathic Pulmonary Fibrosis (2019)
  • Author(s): Moore C, Blumhagen Z, Yang V,Walts A, Powers J, Walker T, Bishop M, Russell P, Vestal B, Cardwell J, Markin CR, Mathai SK, Schwarz MI, Steele MP, Lee J, Brown KK, Loyd JE, Crapo JD, Silverman EK, Cho MH, et al.
  • Journal Title: American Journal of Respiratory and Critical Care Medicine Volume: 印刷中 Issue: 2 Pages: 199-208
  • DOI: 10.1164/rccm.201810-1891oc
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Nrf2 Suppresses Allergic Lung Inflammation by Attenuating the Type 2 Innate Lymphoid Cell Response (2019)
  • Author(s): Nagashima Ryuichi、Kosai Hitomi、Masuo Masahiro、Izumiyama Keiko、Noshikawaji Taketo、Morimoto Motoko、Kumaki Satoru、Miyazaki Yasunari、Motohashi Hozumi、Yamamoto Masayuki、Tanaka Nobuyuki
  • Journal Title: The Journal of Immunology Volume: 202 Issue: 5 Pages: 1331-1339
  • DOI: 10.4049/jimmunol.1801180
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Periostin as a predictor of prognosis in chronic bird-related hypersensitivity pneumonitis (2019)
  • Author(s): Nukui Yoshihisa、Miyazaki Yasunari、Masuo Masahiro、Okamoto Tsukasa、Furusawa Haruhiko、Tateishi Tomoya、Kishino Mitsuhiro、Tateishi Ukihide、Ono Junya、Ohta Shoichiro、Izuhara Kenji、Inase Naohiko
  • Journal Title: Allergology International Volume: 68 Issue: 3 Pages: 363-369
  • DOI: 10.1016/j.alit.2019.02.007
  • NAID: 130007678459
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Treatment of asthma in smokers: A questionnaire survey in Japanese clinical practice (2019)
  • Author(s): Saito H, Tsuchiya K, Chiba S, Ogata T, Imase R, Yagi T, Mishima Y, Jinta T, Saito K, Taki R, Isogai S, Jin Y, Kawasaki T, Natsume I, Miyashita Y, Takagiwa J, Ishiwata N, Chiaki T, Kishi M, Tsukada Y, Yamasaki M, Inase N, Miyazaki Y.
  • Journal Title: Respiratory Investigation Volume: 57 Issue: 2 Pages: 126-132
  • DOI: 10.1016/j.resinv.2018.11.001
  • Peer Reviewed
• [Journal Article] Acute inflammatory and immunologic responses against antigen in chronic bird-related hypersensitivity pneumonitis (2019)
  • Author(s): Inoue Yukihisa、Ishizuka Masahiro、Furusawa Haruhiko、Honda Takayuki、Kawahara Tatsuo、Tateishi Tomoya、Miyazaki Yasunari
  • Journal Title: Allergology International Volume: 68 Issue: 3 Pages: 321-328
  • DOI: 10.1016/j.alit.2018.12.010
  • NAID: 130007678449
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Coexistence of dementia with smear-positive pulmonary tuberculosis is associated with patient in-hospital mortality (2019)
  • Author(s): Saiki Masafumi、Iijima Yuki、Honda Takayuki、Mori Sayaka、Tsutsui Toshiharu、Uchida Yoshinori、Kobayashi Yoichi、Kakizaki Yumiko、Sakashita Hiroyuki、Miyazaki Yasunari、Miyashita Yoshihiro
  • Journal Title: Respiratory Investigation Volume: 印刷中 Issue: 4 Pages: 354-360
  • DOI: 10.1016/j.resinv.2019.01.004
  • Peer Reviewed
• [Journal Article] Ablation of miR-146b in mice causes hematopoietic malignancy (2018)
  • Author(s): Mitsumura Takahiro、Ito Yoshiaki、Chiba Tomoki、Matsushima Takahide、Kurimoto Ryota、Tanaka Yoko、Kato Tomomi、Uchida Keisuke、Ito Takashi、Yamamoto Kouhei、Eishi Yoshinobu、Kitagawa Masanobu、Miyazaki Yasunari、Inase Naohiko、Asahara Hiroshi
  • Journal Title: Blood Advances Volume: 2 Issue: 23 Pages: 3483-3491
  • DOI: 10.1182/bloodadvances.2018017954
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Acute exacerbations of progressive-fibrosing interstitial lung diseases (2018)
  • Author(s): Kolb Martin、Bondue Benjamin、Pesci Alberto、Miyazaki Yasunari、Song Jin Woo、Bhatt Nitin Y.、Huggins John T.、Oldham Justin M.、Padilla Maria L.、Roman Jesse、Shapera Shane
  • Journal Title: European Respiratory Review Volume: 27 Issue: 150 Pages: 180071-180071
  • DOI: 10.1183/16000617.0071-2018
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Evidence of latent molecular diversity determining the virulence of community-associated MRSA USA300 clones in mice (2018)
  • Author(s): Sonoda Shiro、Yamaguchi Tetsuo、Aoki Kotaro、Ono Daisuke、Sato Ayami、Kajiwara Chiaki、Kimura Soichiro、Akasaka Yoshikiyo、Ishii Yoshikazu、Miyazaki Yasunari、Inase Naohiko、Tateda Kazuhiro
  • Journal Title: Immunity, Inflammation and Disease Volume: 6 Issue: 3 Pages: 402-412
  • DOI: 10.1002/iid3.234
  • Peer Reviewed
• [Journal Article] Environmental levels of avian antigen are relevant to progression of chronic hypersensitivity pneumonitis during antigen avoidance. (2018)
  • Author(s): Sema M, Miyazaki Y, Tsutsui T, Tomita M, Eishi Y, Inase N.Sema M, Miyazaki Y, Tsutsui T, Tomita M, Eishi Y, Inase N.
  • Journal Title: Immun Inflamm Dis. Volume: 6 Issue: 1 Pages: 154-162
  • DOI: 10.1002/iid3.202
  • Peer Reviewed
• [Journal Article] The immune checkpoint molecule VISTA regulates allergen-specific Th2-mediated immune responses. (2018)
  • Author(s): Ohno T, Zhang C, Kondo Y, Kang S, Furusawa E, Tsuchiya K, Miyazaki Y, Azuma M.
  • Journal Title: Int Immunol. Volume: 30 Issue: 1 Pages: 3-11
  • DOI: 10.1093/intimm/dxx070
  • Peer Reviewed
• [Journal Article] Histological variability and consequences in chronic bird-related hypersensitivity pneumonitis. (2017)
  • Author(s): Ochi J, Ohtani Y, Takemura T, Akashi T, Tateishi T, Miyazaki Y, Inase N, Yoshizawa Y.
  • Journal Title: Respirology. Volume: 22 Issue: 7 Pages: 1350-1356
  • DOI: 10.1111/resp.13070
  • Peer Reviewed
• [Journal Article] Protein antigen of bird-related hypersensitivity pneumonitis in pigeon serum and dropping. (2017)
  • Author(s): Shirai T, Furusawa H, Furukawa A, Ishige Y, Uchida K, Miyazaki Y, Eishi Y, Inase N.
  • Journal Title: Respiratory Research Volume: 18 Issue: 1 Pages: 65-65
  • DOI: 10.1186/s12931-017-0555-4
  • Peer Reviewed
• [Journal Article] Histological variability and consequences in chronic bird-related hypersensitivity pneumonitis. (2017)
  • Author(s): Ochi J, Ohtani Y, Takemura T, Akashi T, Tateishi T, Miyazaki Y, Inase N, Yoshizawa Y.
  • Journal Title: Respirology Volume: 印刷中
  • Peer Reviewed
• [Presentation] Role of Lung Apolipoprotein A-I in Hypersensitivity Pneumonitis (2018)
  • Author(s): Inoue Y., Miyazaki Y., Nukui Y., Inase N.
  • Organizer: American Thoracic Society
  • Int'l Joint Research
• [Presentation] Serum Angiopoietin-2 Can Be A Biomarker In Acute Exacerbation Of Interstitial Pneumonia (2018)
  • Author(s): Tateishi T., Fujie T., Saito H., Miyazaki Y., Inase N.
  • Organizer: American Thoracic Society
• [Presentation] The Role of Forced Oscillation Technique to Diagnose Patients with Cough Variant Asthma (2018)
  • Author(s): Koike F., Otani Y., Oyama S., Furuie W., Endo J., Nakamura Y., Akaza M., Sasano T., Miyazaki Y., Inase N., Sumi Y.
  • Organizer: American Thoracic Society
• [Presentation] 鳥関連過敏性肺炎における抗原吸入前後のサイトカイン・ケモカインの検討 (2018)
  • Author(s): 井上幸久, 石塚聖洋, 古澤春彦, 白井剛, 増尾昌宏, 立石知也, 藤江俊秀, 玉岡明洋, 坂下博之, 稲瀬直彦, 宮崎泰成
  • Organizer: 日本呼吸器学会学術集会
• [Book] いびき!?眠気!?睡眠時無呼吸症を疑ったら (2018)
  • Author(s): 宮崎 泰成
  • Total Pages: 269
  • Publisher: 羊土社
  • ISBN: 9784758118347
• [Book] Annual Review 2016呼吸器 (2016)
  • Author(s): 宮崎泰成 岡本師 稲瀬直彦
  • Total Pages: 238
  • Publisher: 中外医薬社