Investigation of the role of regulatory T cells in atherosclerotic disease

• Project/Area Number: 25860601
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Kobe University
• Principal Investigator: SASAKI NAOTO 神戸大学, 医学(系)研究科(研究院), 助教 (00514746)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 動脈硬化症 / 炎症 / 免疫細胞

Outline of Final Research Achievements

We provided direct evidence that regulatory T cells (Tregs) prevent atherosclerotic disease by dampening pathogenic immune responses. We also demonstrated that promotion of an endogenous regulatory immune response could be a possible therapeutic approach to prevent the development of atherosclerosis and abdominal aortic aneurysm and induce regression of established atherosclerosis in mice.

Research Products

• [Journal Article] Foxp3+ regulatory T cells play a protective role in angiotensin II-induced aortic aneurysm formation in mice. (2015)
  • Author(s): Yodoi K, Yamashita T, Sasaki N, Kasahara K, Emoto T, Matsumoto T, Kita T, Sasaki Y, Mizoguchi T, Sparwasser T, Hirata K.
  • Journal Title: Hypertension Volume: 65 Issue: 4 Pages: 889-895
  • DOI: 10.1161/hypertensionaha.114.04934
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Regulatory T cells and tolerogenic dendritic cells as critical immune modulators in atherogenesis. (2015)
  • Author(s): Sasaki N, Yamashita T, Kasahara K, Takeda M, Hirata K.
  • Journal Title: Current Pharmaceutical Design Volume: 21 Pages: 1107-1117
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The regulatory / effector T cell ratio is reduced in coronary artery disease. (2014)
  • Author(s): Emoto T, Sasaki N, Yamashita T, Kasahara K, Yodoi K, Sasaki Y, Matsumoto T, Mizoguchi T, Hirata K.
  • Journal Title: Circulation Journal Volume: 78 Pages: 2935-2941
  • NAID: 130004699205
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] CD3 antibody and IL-2 complex combination therapy inhibits atherosclerosis by augmenting a regulatory immune response. (2013)
  • Author(s): Kasahara K, Sasaki N, Yamashita T, Kita T, Yodoi K, Sasaki Y, Takeda M, Hirata K.
  • Journal Title: J Am Heart Assoc. Volume: 3 Issue: 2
  • DOI: 10.1161/jaha.113.000719
  • Peer Reviewed / Open Access
• [Journal Article] Regression of atherosclerosis with anti-CD3 antibody via augmenting a regulatory T-cell response in mice. (2013)
  • Author(s): Kita T, Yamashita T, Sasaki N, Kasahara K, Sasaki Y, Yodoi K, Takeda M, Nakajima K, Hirata K.
  • Journal Title: Cardiovasc Res. Volume: 102 Issue: 1 Pages: 107-117
  • DOI: 10.1093/cvr/cvu002
  • Peer Reviewed
• [Presentation] Regulatory T cells and CD4+CD28null T cells in coronary artery disease (2014)
  • Author(s): Takuo Emoto, Naoto Sasaki, Tomoya Yamashita, Kazuyuki Kasahara, Keiko Yodoi, Yoshihiro Sasaki, Takuya Matsumoto, Taiji Mizoguchi, Ken-ichi Hirata
  • Organizer: 第46回日本動脈硬化学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] Gut microbiota modulates coronary atherogenesis (2014)
  • Author(s): Takuo Emoto, Naoto Sasaki, Tomoya Yamashita, Kazuyuki Kasahara, Keiko Yodoi, Yoshihiro Sasaki, Takuya Matsumoto, Taiji Mizoguchi, Ken-ichi Hirata
  • Organizer: 第46回日本動脈硬化学会総会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] 抗CD3抗体とIL-2複合体の併用療法は、アポE欠損マウスにおけるエフェクターT細胞と制御性T細胞のバランスを変化させ、動脈硬化を抑制する (2014)
  • Author(s): Kazuyuki Kasahara, Naoto Sasaki, Tomoya Yamashita, Yoshihiro Sasaki, Keiko Yodoi, Takuo Emoto, Takuya Matsumoto, Ken-ichi Hirata
  • Organizer: 第43回日本心血管作動物質学会
  • Place of Presentation: 神戸
• [Presentation] アンジオテンシンII負荷腹部大動脈瘤マウスモデルにおける制御性T細胞の役割の検討 (2014)
  • Author(s): Keiko Yodoi, Tomoya Yamashita, Naoto Sasaki, Tomoyuki Kita, Kazuyuki Kasahara, Yoshihiro Sasaki, Takuo Emoto, Takuya Matsumoto, Taiji Mizoguchi, Ken-ichi Hirata
  • Organizer: 第43回日本心血管作動物質学会
  • Place of Presentation: 神戸
• [Presentation] Activation of skin dendritic cells controls atherogensis in mice
  • Author(s): Naoto Sasaki, Tomoya Yamashita, Kazuyuki Kasahara, Tomoyuki Kita, Yoshihiro Sasaki, Keiko Yodoi, Takuo Emoto, Takuya Matsumoto, Ken-ichi Hirata
  • Organizer: 第45回日本動脈硬化学会総会
  • Place of Presentation: 東京
• [Presentation] The balance between regulatory T cells and effector T cells is important for the control of atherosclerosis
  • Author(s): Kazuyuki Kasahara, Tomoya Yamashita, Naoto Sasaki, Yoshihiro Sasaki, Keiko Yodoi, Ken-ichi Hirata
  • Organizer: 第45回日本動脈硬化学会総会
  • Place of Presentation: 東京
• [Presentation] The effects in vivo expansion of regulatory T cells on abdominal aortic aneurysm in the angiotensin II-induced murine model
  • Author(s): Keiko Yodoi, Tomoya Yamashita, Naoto Sasaki, Tomoyuki Kita, Kazuyuki Kasahara, Yoshihiro Sasaki, Takuo Emoto, Takuya Matsumoto, Ken-ichi Hirata
  • Organizer: 第45回日本動脈硬化学会総会
  • Place of Presentation: 東京
• [Presentation] Regression of atherosclerosis with anti-CD3 antibody via modulating the ratio of effector and regulatory T cells in mice
  • Author(s): Yoshihiro Sasaki, Naoto Sasaki, Tomoya Yamashita, Tomoyuki Kita, Kazuyuki Kasahara, Keiko Yodoi, Ken-ichi Hirata
  • Organizer: 第45回日本動脈硬化学会総会
  • Place of Presentation: 東京
• [Presentation] Activation of skin dendritic cells controls atherogensis in mice
  • Author(s): Naoto Sasaki, Tomoya Yamashita, Kazuyuki Kasahara, Tomoyuki Kita, Yoshihiro Sasaki, Keiko Yodoi, Ken-ichi Hirata
  • Organizer: 第86回米国心臓学会議
  • Place of Presentation: ダラス（アメリカ合衆国）
• [Presentation] A novel combination therapy with anti-CD3 antibody and IL-2 complexes against atherosclerosis targeting effector T cells and regulatory T cells
  • Author(s): Kazuyuki Kasahara, Tomoya Yamashita, Naoto Sasaki, Yoshihiro Sasaki, Keiko Yodoi, Ken-ichi Hirata
  • Organizer: 第86回米国心臓学会議
  • Place of Presentation: ダラス（アメリカ合衆国）
• [Presentation] In vivo expansion of regulatory T cells attenuates aortic aneurysm formation in angiotensin II- infused apolipoprotein E-deficient mice
  • Author(s): Keiko Yodoi, Naoto Sasaki,Taiji Mizoguchi, Takuya Matsumoto, Takuo Emoto, Yoshihiro Sasaki, Kazuyuki Kasahara, Tomoyuki Kita, Tomoya Yamashita, Ken-ichi Hirata
  • Organizer: 第86回米国心臓学会議
  • Place of Presentation: ダラス（アメリカ合衆国）
• [Presentation] 免疫制御による動脈硬化性疾患予防・治療戦略
  • Author(s): 佐々木直人、山下智也、平田健一
  • Organizer: 第43回日本心血管作動物質学会
  • Place of Presentation: 神戸
• [Presentation] Regulation of Pathogenic Inflammatory Responses via Modulating Skin Immune System for Prevention of Atherosclerosis
  • Author(s): Naoto Sasaki, Tomoya Yamashita, Kazuyuki Kasahara, Yoshihiro Sasaki, Keiko Yodoi, Ken-ichi Hirata
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京
• [Presentation] Anti-CD3 antibody and interleukin-2 complex combination therapy inhibits atherosclerosis development by dramatically augmenting a regulatory immune response
  • Author(s): Kazuyuki Kasahara, Naoto Sasaki, Tomoya Yamashita, Yoshihiro Sasaki, Keiko Yodoi, Ken-ichi Hirata
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京
• [Presentation] Regulatory T Cells Play a Protective Role in Angiotensin II-Induced Aortic Aneurysm Formation
  • Author(s): Keiko Yodoi, Tomoya Yamashita, Naoto Sasaki, Kazuyuki Kasahara, Yoshihiro Sasaki, Takuo Emoto, Takuya Matsumoto,Taiji Mizoguchi, Ken-ichi Hirata
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京
• [Presentation] The effector/ regulatory T cell ratio is reduced in coronary artery disease
  • Author(s): Takuo Emoto, Naoto Sasaki, Taiji Mizoguchi, Takuya Matsumoto, Keiko Yodoi, Yoshihiro Sasaki, Kazuyuki Kasahara, Tomoya Yamashita, Ken-ichi Hirata
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京
• [Book] 医学のあゆみ (2013)
  • Author(s): 佐々木直人、平田健一
  • Total Pages: 118
  • Publisher: 医歯薬出版株式会社
• [Remarks] 神戸大学大学院医学研究科 循環器内科学分野
  • URL: http://www.med.kobe-u.ac.jp/im1/index.html