Interleukin-17 Accelerates Allograft Rejection by Suppressing Regulatory T Cell Expansion

• Project/Area Number: 23791573
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Thoracic surgery
• Research Institution: Jichi Medical University
• Principal Investigator: ITOH Satoshi 自治医科大学, 医学部, 講師 (30382881)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 心臓移植 / インターロイキン １７ / 移植免疫 / 急性拒絶応答 / インタロイキン１７ / 移植片拒絶応答 / 国際情報交換 / 国際情報交流

Research Abstract

Interleukin-17 (IL-17), which is predominantly produced by T helper 17 cells distinct from T helper 1 or T helper 2 cells, participates in the pathogenesis of infectious, autoimmune, and allergic disorders. However, the precise role in allograft rejection remains uncertain. In the present study, we investigated the role of IL-17 in acute allograft rejection using IL-17-deficient mice.
During heart transplantation, (1) IL-17 is crucial for acceleration of acute rejection; (2) IL-17-deficiency enhances regulatory T cell expansion; and (3) gamma delta T cells rather than CD4 T and CD8 T cells are a potential source of IL-17. IL-17 neutralization may provide a potential target for novel therapeutic treatment for cardiac allograft rejection.

Research Products

• [Journal Article] Utility of the Penn classification in predicting outcomes of surgery for acute type a aortic dissection. (2014)
  • Author(s): Kimura N, Ohnuma T, Itoh S, Sasabuchi Y, Asaka K, Shiotsuka J, Adachi K, Yuri K, Matsumoto H, Yamaguchi A, Sanui M, Adachi H.
  • Journal Title: Am J Cardiol Volume: 113(4) Pages: 724-730
  • Peer Reviewed
• [Journal Article] Potential role ofγδT cell-derived IL-17 in acute cardiac allograft rejection (2012)
  • Author(s): Kimura N, Nakae S, Itoh S, Merk DR, Wang X, Gong Y, Okamura H, Chang PA, Adachi H, Robbins RC, Fischbein MP.
  • Journal Title: Ann Thorac Surg Volume: 94(2) Issue: 2 Pages: 542-8
  • DOI: 10.1016/j.athoracsur.2012.03.049
  • Peer Reviewed
• [Journal Article] Potential role of γδ T cell-derived IL-17 in acute cardiac allograft rejection. (2012)
  • Author(s): Kimura N, Nakae S, Itoh S, Merk DR, Wang X, Gong Y, Okamura H, Chang PA, Adachi H, Robbins RC, Fischbein MP.
  • Journal Title: Ann Thorac Surg Volume: 94(2) Pages: 542-8
  • Peer Reviewed
• [Journal Article] Interleukin-16 deficiency suppresses the development of chronic rejection in murine cardiac transplantation model (2011)
  • Author(s): Itoh S, Kimura N, Nakae S, Axtell RC, Velotta JB, Bos EJ, Merk DR, Gong Y, Okamura H, Nagamine CM, Adachi H, Kornfeld H, Robbins RC, Fischbein MP.
  • Journal Title: J Heart Lung Transplant Volume: 30(12) Issue: 12 Pages: 1409-17
  • DOI: 10.1016/j.healun.2011.08.017
  • Peer Reviewed
• [Journal Article] Interleukin-17 accelerates allograft rejection by suppressing regulatory T cell expansion (2011)
  • Author(s): S.Itoh
  • Journal Title: Circulation Volume: 124 Issue: 11_suppl_1
  • DOI: 10.1161/circulationaha.110.014852
  • Peer Reviewed
• [Journal Article] IL-17 Accelerates Allograft Rejection by Suppressing Regulatory T Cell Expansion. (2011)
  • Author(s): Itoh S, Kimura N, Axtell RC, Velotta JB, Gong Y, Wang X, Kajiwara N, Nambu A, Shimura N, Adachi H, Iwakura Y, Saito H, Okumura K, Sudo K, Steinman L, Robbins RC, Nakae S, Fischbein MP.
  • Journal Title: Circulation Volume: 124
  • Peer Reviewed
• [Journal Article] Interleukin-16 deficiency suppresses the development of chronic rejection in murine cardiac transplantation model (2011)
  • Author(s): Kimura N, Itoh S, Nakae S, Axtell RC, Velotta JB, Bos EJ, Merk DR, Gong Y,Okamura H, Nagamine CM, Adachi H, Kornfeld H, Robbins RC, Fischbein MP
  • Journal Title: Journal of Heart and Lung Transplantation Volume: 30 Pages: 1409-17
  • Peer Reviewed
• [Presentation] (2014)
  • Organizer: 第44回日本心臓血管外科学術総会
  • Place of Presentation: 熊本
• [Presentation] 急性冠症候群（ACS）に対するCABG (2014)
  • Author(s): 伊藤 智，山口敦司，木村直行，由利康一，安達晃一，安達秀雄
  • Organizer: 第44回日本心臓血管外科学会定期学術総会
  • Place of Presentation: 熊本
• [Presentation] (2013)
  • Organizer: 第66回日本胸部外科学会定期学術集会
  • Place of Presentation: 仙台
• [Presentation] (2013)
  • Organizer: 第27回日本冠疾患学会学術集会
  • Place of Presentation: 和歌山
• [Presentation] 心室中隔穿孔に対する外科治療の遠隔期成績． (2013)
  • Author(s): 伊藤 智，山口敦司，野口権一郎，田中正史，木村直行，由利康一，安達晃一，安達秀雄
  • Organizer: 第27回日本冠疾患学会学術集会
  • Place of Presentation: 和歌山
• [Presentation] 狭小大動脈弁輪を呈する大動脈弁狭窄症症例に対するTrifecta弁の有用性―急性期治療成績の検討． (2013)
  • Author(s): 伊藤 智，木村直行，田中正史，野口健一郎，片山郁夫，由利康一，松本春信，安達晃一，山口敦司，安達秀雄．
  • Organizer: 第66回日本胸部外科学会定期学術集会
  • Place of Presentation: 仙台
• [Presentation] (2012)
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: 福岡
• [Presentation] Interleukin-16 deficiency suppresses the development of chronic rejection in murine cardiac transplantation model. (2012)
  • Author(s): Kimura N, Itoh S, Nakae S, Okamura H, Adachi H, Robbins RC, Fischbein MP.
  • Organizer: 第65回日本胸部外科学会定期学術集会
  • Place of Presentation: 福岡