Elucidation of pathophysiology of chronic rejection after lung transplantation and development of a novel therapeutic method through IL-17 pathway.

• Project/Area Number: 16K10418
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Tohoku University
• Principal Investigator: MATSUDA YASUSHI 東北大学, 大学病院, 助教 (00455833)
• Co-Investigator(Kenkyū-buntansha): 桜田 晃 東北大学, 加齢医学研究所, 准教授 (60360872) ; 野田 雅史 東北大学, 大学病院, 講師 (70400356) ; 渡邉 龍秋 東北大学, 加齢医学研究所, 非常勤講師 (70636034) ; 岡田 克典 東北大学, 加齢医学研究所, 教授 (90323104) ; 星川 康 藤田医科大学, 医学部, 教授 (90333814)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 慢性拒絶反応 / 肺移植 / IL-17 / 肺内リンパ新生 / リンパ新生 / 肺内気管移植モデル / 肺移植後 / 気道閉塞 / ヘルパーT細胞 / 移植外科

Outline of Final Research Achievements

We used abatacept to suppress Th17 cells that produce IL-17, and intrapulmonary tracheal transplantation as a model of bronchiolitis obliterans syndrome. We examined the obstruction of transplanted trachea, lymphoid neogenesis. The treatment of IL 17 suppression attenuated the area of lymphoid neogenesis around transplanted trachea in the lung and obstraction ratio of inner of transplanted trachea, comapred to control. According to the results, Suppression of IL-17 with the inhibitor should be one of novel treatment of bronchiolitis obliterans syndrome, which is one of major complication after lung transplantation.

Academic Significance and Societal Importance of the Research Achievements

脳死肺移植の現状では、肺移植後5年生存率が約55％と限られている。日本での肺移植後の長期生存症例では、慢性拒絶反応としての閉塞制裁気管支炎(bronchiolitis obliterans syndrome:BOS)によって、呼吸機能が低下し死亡に至る。肺移植後の予後を改善するためBOSの治療およびコントロールが必須となっている。今回の実験結果によりIL-17がBOSの病態悪化の原因の一つとなっていることが判明し、IL-17の発現を抑制することでBOSの病勢コントロールが可能となることが示唆された。これは今後増加する肺移植の予後を改善するものであり、今後実臨床に役立てられると考えられる。

Research Products

• [Journal Article] Detection of engraftment of donor-derived antibody producing cells in a lung transplant recipient by anti-cytomegalovirus IgG avidity test (2019)
  • Author(s): Koshizuka Tetsuo、Matsuda Yasushi、Suzuki Hirotoshi、Kanno Ryoko、Ikuta Kazufumi、Kobayashi Takahiro、Kondo Takashi、Okada Yoshinori、Suzutani Tatsuo
  • Journal Title: Transplant Immunology Volume: 53 Pages: 34-37
  • DOI: 10.1016/j.trim.2018.12.003
  • Peer Reviewed
• [Journal Article] Correlation between the native lung volume change and postoperative pulmonary function after single lung transplantation for lymphangioleiomyomatosis: Evaluation of lung volume by three-dimensional computed tomography volumetry. (2019)
  • Author(s): Suzuki H, Oishi H, Noda M, Watanabe T, Matsuda Y, Tominaga J, Sado T, Sakurada A, Kurosawa H, Takase K, Okada Y.
  • Journal Title: PLoS One. Volume: 14 Issue: 2 Pages: 0210975-0210975
  • DOI: 10.1371/journal.pone.0210975
  • Peer Reviewed
• [Journal Article] Sustained-Release Tacrolimus Stabilizes Decline of Forced Expiratory Volume in 1 Second Through Decreasing Fluctuation of Its Trough Blood Level (2018)
  • Author(s): Matsuda Y.、Eba S.、Hoshi F.、Oishi H.、Sado T.、Noda M.、Sakurada A.、Watanabe T.、Niikawa H.、Akiba M.、Okada Y.
  • Journal Title: Transplantation Proceedings Volume: 50 Issue: 9 Pages: 2768-2770
  • DOI: 10.1016/j.transproceed.2018.03.039
  • Peer Reviewed
• [Journal Article] Management of De Novo Mycobacterial Infection After Lung Transplantation Without Rifampicin: Case Series of a Single Institution (2018)
  • Author(s): Suzuki H.、Matsuda Y.、Noda M.、Oishi H.、Watanabe T.、Sado T.、Yamada M.、Tamada T.、Okada Y.
  • Journal Title: Transplantation Proceedings Volume: 50 Issue: 9 Pages: 2764-2767
  • DOI: 10.1016/j.transproceed.2018.03.058
  • Peer Reviewed
• [Presentation] CTLA4-Ig therapy attenuates bronchiolitis obliterans after mouse Intrapulmonary tracheal Transplantation model through possibility of effect LAG-3 Tregs (2019)
  • Author(s): Yamato Suzuki, MD, Hisashi Oishi, MD, PhD, Masahiko Kanehira, PhD, Yasushi Matsuda, MD, PhD, Tetsu Sado, MD, PhD, Funahashi Jun-ichi PhD, Akira Sakurada MD, PhD, Yoshinori Okada, MD, PhD
  • Organizer: ISHLT
  • Int'l Joint Research
• [Presentation] Sequential single lung transplantation after contra-lateral single lung transplantation. (2018)
  • Author(s): Yasushi Matsuda1)2), Hisashi Oishi1), Fumihiko Hoshi1), Shunsuke Eba1), Tetsu Sado1), Masafumi Noda1), Akira Sakurada1), Miki Akiba2) Yoshinori Okada1)
  • Organizer: ECTTA
  • Int'l Joint Research