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

2013 Fiscal Year Final Research Report

• 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
• Keywords: 心臓移植 / インターロイキン １７ / 移植免疫 / 急性拒絶応答

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] 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) Pages: 542-8
  • DOI: 10.1016/j.athoracsur.2012.03.049
  • 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) 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): 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(11 ) Pages: S187-96
  • DOI: 10.1161/CIRCULATIONAHA.110.014852.
  • 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
  • Year and Date: 20140219-21
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  • Year and Date: 20131213-14
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  • Organizer: 第76回日本循環器学会学術集会
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