Lymphocyte recruitment analysis by intravital imaging in COPD mouse model

• Project/Area Number: 17K08796
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kansai Medical University
• Principal Investigator: KAMIOKA Yuji 関西医科大学, 医学部, 講師 (50511424)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: COPD / intravital imaging / イメージング / 炎症 / 細胞動態 / Talin-1 / 細胞接着 / Rap1 / 免疫 / 生体肺イメージング / COPDモデル / COPDマウスモデル / 慢性閉塞性肺疾患 / 三次リンパ組織 / TLO

Outline of Final Research Achievements

Tertiary lymphoid tissue（TLO） induced by chronic inflammation has been reported to function as a place for differentiation and interaction of lymphocytes and is deeply involved in pathological conditions in human diseases. However, the mechanism of TLO formation and the recruitment of lymphocytes in TLO have been partially understood based on conventional, immunohistochemical techniques. To solve these questions, it is necessary to analyze the cell dynamics of each TLO in detail. In this study, we aimed to analyze the cell dynamics by directly observing the living lung of a mouse model of chronic obstructive pulmonary disease with a two-photon excitation microscopy.

Academic Significance and Societal Importance of the Research Achievements

COPD初期症状は風邪などと似ているため放置されるケースが多く、COPD初期の臨床データは不足している。またマウスを用いた基礎研究の場合、細胞レベルでのイメージングは呼吸運動による撮影ズレのためにこれまで困難であった。
申請者は、細胞レベルで生体組織を撮影できる二光子励起顕微鏡と、人口呼吸器、真空ポンプを組み合わせることによって、撮影ズレを極力抑えた生体肺イメージングシステムを構築した。本研究は、COPDの初期発生メカニズムおよび悪性化メカニズムを細胞レベルで解明し、COPDの早期発見や悪性化の抑制につながることが期待できる。

Research Products

• [Journal Article] A platform of BRET-FRET hybrid biosensors for optogenetics, chemical screening, and in vivo imaging. (2018)
  • Author(s): Komatsu N, Terai K, Imanishi A, Kamioka Y, Sumiyama K, Jin T, Okada Y, Nagai T, Matsuda M.
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 8984-8984
  • DOI: 10.1038/s41598-018-27174-x
  • NAID: 120006523820
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Roles of Rap1 signaling in lymphocyte homing to peripheral andmucosal lymph nodes (2019)
  • Author(s): Yuji Kamioka
  • Organizer: 第48回日本免疫学会学術集会
• [Presentation] Roles of Rap1, Talin-1 and Kindlin-3 in lymphocyte homing to peripheral and mucosal lymph nodes (2018)
  • Author(s): Kamioka Y, Ueda Y, Kondo N, Kinashi T
  • Organizer: 第47回日本免疫学会学術集会
• [Presentation] Regulation of cell polarization by Rap1 via NDR/Rab8 axis upon chemokine stimulation (2018)
  • Author(s): Ueda Y, Kondo N, Kamioka Y, Kinashi T
  • Organizer: 第47回日本免疫学会学術集会
• [Presentation] Rap1 signaling to NDR1 kinase regulate immune synapse formation and cell polarity. (2018)
  • Author(s): Kinashi T, Kondo N, Ueda Y, Kamioka Y
  • Organizer: The 9th Xiamen Winter Symposium
  • Int'l Joint Research / Invited
• [Presentation] Roles of Rap1 and Kindlin-3 in lymphocyte homing to peripheral lymph nodes (2017)
  • Author(s): Yuji Kamioka
  • Organizer: 第46回日本免疫学会学術集会
• [Remarks] 関西医科大学生命医学研究所 分子遺伝学部門
  • URL: http://www3.kmu.ac.jp/molgent/
• [Remarks] 関西医科大学生命医学研究所分子遺伝学部門
  • URL: http://www3.kmu.ac.jp/molgent/