Elucidation of the mechanism of transplanted rejected airways with special reference to innate immunity

• Project/Area Number: 25462173
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: The University of Tokyo
• Principal Investigator: Murakawa Tomohiro 東京大学, 医学部附属病院, 登録研究員 (50359626)
• Co-Investigator(Kenkyū-buntansha): NAKAJIMA JUN 東京大学, 医学部附属病院, 教授 (90188954) ; NAGAYAMA KAZUHIRO 東京大学, 医学部附属病院, 助教 (00647935) ; 北野 健太郎 東京大学, 医学部附属病院, 助教 (70647073)
• Research Collaborator: MURAYAMA TOMONORI 東京大学, 医学部附属病院 ; KAWASHIMA MITSUAKI 東京大学, 医学部附属病院
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 肺移植 / 閉塞性細気管支炎 / 自然免疫 / 気道リモデリング / 急性肺傷害 / 脳死

Outline of Final Research Achievements

We confirmed that allograft airway fibrosis was reduced in toll-like receptor 4 (TLR4) mutant recipient mouse. This result suggests that not only acquired immunity but also innate immunity including TLR4 signal transduction control allo-immune response and tissue remodeling. In future perspective, using TLR4 inhibitor may be an innovative therapeutic option to reduce allograft airway fibrosis that cannot be inhibited by already established immune-suppressants.

Research Products

• [Journal Article] Fibroblasts of recipient origin contribute to airway fibrosis in murine tracheal transplantations. (2015)
  • Author(s): Konoeda C, Nakajima J, Murakawa T.
  • Journal Title: Transpl Int Volume: 28 Issue: 6 Pages: 761-763
  • DOI: 10.1111/tri.12525
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Epithelial to Mesenchymal Transition in Murine Tracheal Allotransplantation: An Immunohistochemical Observation. (2013)
  • Author(s): Chihiro Konoeda
  • Journal Title: Transplantation Proceedings Volume: - Issue: 5 Pages: 1797-1801
  • DOI: 10.1016/j.transproceed.2012.11.024
  • Peer Reviewed
• [Journal Article] The ground glass opacity component can be eliminated from the T-factor assessment of lung adenocarcinoma. (2013)
  • Author(s): Tomohiro Murakawa, Chihiro Konoeda,Takuya Ito, Yuta Inoue, Atsushi Sano, Kazuhiro Nagayama, Jun Nakajima.
  • Journal Title: European journal of cardio-thoracicsurgery. Volume: 43(5) Issue: 5 Pages: 925-932
  • DOI: 10.1093/ejcts/ezs467
  • Peer Reviewed
• [Journal Article] Ex vivo characterization of γδ T-cell repertoire in patients after adoptive transfer of Vγ9Vδ2 T cells expressing the interleukin-2 receptor β-chain andthe common γ-chain. (2013)
  • Author(s): Izumi T, Kondo M, Takahashi T, Fujieda N, Kondo A, Tamura N, Murakawa T, Nakajima J, Matsushita H, Kakimi K.
  • Journal Title: Cytotherapy Volume: 15(4) Issue: 4 Pages: 481-491
  • DOI: 10.1016/j.jcyt.2012.12.004
  • Peer Reviewed
• [Journal Article] Chest wall deformity found in patients with primary spontaneous pneumothorax. (2013)
  • Author(s): Saita K, Murakawa T, Kawano H, Sano A, Nagayama K, Nakajima J.
  • Journal Title: Asian Cardiovascular and Thoracic Annals Volume: 21 Issue: 5 Pages: 582-587
  • DOI: 10.1177/0218492312467174
  • Peer Reviewed
• [Presentation] Circulating histone-induced lung injury: a novel model of damaged lungs from brain-dead donors. (2015)
  • Author(s): Murayama T, Anraku M, Murakawa T, Yoshioka T, Inui M, Hiyama N, Kawashima M, Tsuchiya T, Ichinose J, Hino H, Nagayama K, Nitadori J, Kakimi K, Nakajima J.
  • Organizer: 35th ISHLT annual meeting and scientific sessions.
  • Place of Presentation: Nice, France
  • Year and Date: 2015-04-15
  • Int'l Joint Research
• [Presentation] 急性グラフと不全モデルの作成 –ラットによるヒストン肺傷害モデル (2014)
  • Author(s): 村山智紀、安樂真樹、唐崎隆弘、一瀬淳二、井上雄太、日野春秋、北野健太郎、長山和弘、似鳥純一、村川知弘、中島淳
  • Organizer: 第30回 肺および心肺移植研究会
  • Place of Presentation: 京都大学芝蘭館稲森ホール
• [Presentation] Origin of fibroblasts in rejected airway: experiment with orthotopic tracheal allotransplantation model using transgenic GFP mice (2013)
  • Author(s): Konoeda C,Koinuma D, Morishita Y, Kitano K, Nagayama K, Anraku M, Kakimi K, Miyazono K, Nakajima J, Murakawa T
  • Organizer: 33rd ISHLT annual meeting and scientific sessions
  • Place of Presentation: Montréal, Canada
• [Remarks] 東京大学医学部附属病院 呼吸器外科 ホームページ
  • URL: http://cts.m.u-tokyo.ac.jp/thoracic-surgery
• [Remarks] 東京大学医学部附属病院 心臓外科・呼吸器外科
  • URL: http://ctstokyo.umin.ne.jp