Development of a novel procedure targeting NKT cells facilitating successful clinical islet transplantation

• Project/Area Number: 18390354
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Fukuoka University
• Principal Investigator: YASUNAMI Yohichi Fukuoka University, 医学部, 教授 (00166521)
• Co-Investigator(Kenkyū-buntansha): NAKANO Masahiko 福岡大学, 医学部, 助教 (90389354) ; MATSUOKA Nobuhide 福岡大学, 医学部, 助教 (40461503) ; HABE Shigehisa 福岡大学, 医学部, 講師 (70037430) ; 笠 普一朗 福岡大学, 医学部, 助手 (30279286)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥17,870,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥3,270,000); Fiscal Year 2008: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000); Fiscal Year 2007: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2006: ¥3,700,000 (Direct Cost: ¥3,700,000)
• Keywords: インスリン依存糖尿病 / 膵島移植 / 自然免疫拒絶反応 / NKT細胞 / 好中球 / HMGB1 / IFN-γ / 拒絶反応 / 炎症性サイトカイン / 移植膵島障害 / 糖尿病 / 組織・細胞

Research Abstract

現在の臨床膵島移植では1人の糖尿病レシピエントの治療に2~3人分のドナー膵臓が必要である。我々は移植早期(24時間以内)に発現する自然免疫拒絶反応による移植膵島破壊がこの問題の本質であると考え、本研究課題を遂行した。その結果、NKT細胞、好中球、炎症性サイトカインが関与する拒絶反応の機序と制御法を明らかにすることができた。本研究成果は臨床膵島移植の成績向上に大きく寄与すると考えられる。

Research Products

• [Journal Article] NKT細胞研究の新展開 : 障島移植拒絶反応とNKT細胞 (2008)
  • Author(s): 安波洋一
  • Journal Title: 医学のあゆみ 225(2) Pages: 151-155
• [Journal Article] The immunoregulatory role of NKT cells in cyclophosphamide-induced tolerance (2007)
  • Author(s): Iwai T, Tomita Y, Kajiwara T, Onzuka T, Okano S, Yasunami Y, Yoshikai Y, Nomoto K, Tominaga R.
  • Journal Title: Transplantation 84(12) Pages: 1686-95
  • Peer Reviewed
• [Journal Article] Successful islet transplantation to two recipients from a single donor by targeting pro-inflammatory cytokines in mice (2007)
  • Author(s): M Satoh, Y Yasunami, N Matsuoka, M Nakano, T Itoh, T Nitta, K Anzai, J Ono, M Taniguchi, S Ikeda
  • Journal Title: Transplantation 83(8) Pages: 1085-1092
  • Peer Reviewed
• [Journal Article] Effects of cyclosporin A on the activation of NKT cells induced by α-galactosylceramide (2007)
  • Author(s): T Kajiwara, Y Tomita, S Okano, T Iwai, Y Yasunami, Y Yoshikai, K Nomoto, R Tominaga, H Yasui
  • Journal Title: Transplantation 83 Pages: 184-192
  • Peer Reviewed
• [Journal Article] Effects of cyclosporin A on the activation of NKT cells induced by α-galactosylceramide (2007)
  • Author(s): T Kajiwara, Y Tomita, S Okano, T Iwai, Y Yasunami, et. al.
  • Journal Title: Transplantation 83 Pages: 184-192
  • Peer Reviewed
• [Journal Article] Successful islet transplantation to two recipients from a single donor by targeting pro-inflammatory cytokines in mice (2007)
  • Author(s): M Satoh, Y Yasunami, et. al.
  • Journal Title: Transplantation 83 Pages: 1085-1092
  • Peer Reviewed
• [Journal Article] The immunoregulatory role of NKT cells in cyclophosphamide-induced tolerance (2007)
  • Author(s): Iwai T, Tomita Y, Kajiwara T, Onzuka T, Okano S, Yasunami Y, et. al.
  • Journal Title: Transplantation 83 Pages: 1686-1695
  • Peer Reviewed
• [Journal Article] Effects of cyclosporin A on the activation of NKT cells induced by α-galactosylceramide (2007)
  • Author(s): T Kajiwara, Y Tomita, S Okano, T Iwai, Y Yasunami, et al.
  • Journal Title: Transplantation In press
• [Journal Article] Successful islet transplantation to two recipients from a single donor by targeting pro-inflammatory cytokines in mice (2007)
  • Author(s): Masayuki Satoh, Yohichi Yasunami, et al.
  • Journal Title: Transplantation In press
• [Journal Article] Regulatory roles of NKT cells in the induction and maintenance of cyclophosphamide-induced tolerance (2006)
  • Author(s): T Iwai, Y Tomita, I Shimizu, Y Yasunami, T Kajiwara, S Okano, M Yoshikai, M Taniguchi, K Nomoto, H Yasui
  • Journal Title: J Immunol 177 Pages: 8400-8409
  • Peer Reviewed
• [Journal Article] NKT cells participate in rejection of islet ablografts in the liver of mice (2006)
  • Author(s): A Toyofuku, Y Yasunami, K Nabeyama, M Nakano, M Satoh, N Matsuoka, J Ono, T Nakayama, M Taniguchi, M Tanaka, S Ikeda
  • Journal Title: Diabetes 55 Pages: 34-39
  • Peer Reviewed
• [Journal Article] Regulatory roles NKT cells in the induction and maintenance of cyclophosphamide-induced tolerance (2006)
  • Author(s): T Iwai, Y Tomita, I Shimizu, Y Yasunami, et al.
  • Journal Title: Journal of Immunology 177・12 Pages: 8400-8409
• [Journal Article] Prevention of early loss of transplanted islets in the liver of mice by adenosine
  • Author(s): T Nitta, T Itoh, N Matsuoka, T Mera, D Kojima, M Nakano, Y Yamashita, Y Yasunami
  • Journal Title: Transplantation (in press) Pages: 0-0
  • Peer Reviewed
• [Journal Article] Prevention of early loss of transplanted islets in the Liver of mice by adenosine
  • Author(s): T Nitta, T Itoh, N Matsuoka, T Mera, D Kojima, M Nakano, Y Yamashita, Y Yasunami
  • Journal Title: Transplantation (In press)
  • Peer Reviewed
• [Presentation] (世話人講演)膵島移植とともに30年、今後の展開 (2009)
  • Author(s): 安波洋一
  • Organizer: 第36回膵・膵島移植研究会
  • Place of Presentation: 福岡
• [Presentation] 移植膵島からHMGB1が放出され早期グラフト障害を惹起する (2009)
  • Author(s): 伊東威, 新田智之, 米良利之, 小島大望, 松岡信秀, 中野昌彦, 金城亜哉, 山下裕一, 安波洋一
  • Organizer: 第36回膵・膵島移植研究会
  • Place of Presentation: 福岡
• [Presentation] (特別講演)膵島移植 ; 今後の展開 (2008)
  • Author(s): 安波洋一
  • Organizer: 第13回糖尿病医学研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-09-26
• [Presentation] 移植早期膵島障害に対するアデノシンの効果-one donor-one recipientの実現に向けて- (2008)
  • Author(s): 新田智之, 伊東威, 米良利之, 小島大望, 中野昌彦, 松岡信秀, 金城亜哉, 山下裕一, 安波洋一
  • Organizer: 第7回日本組織移植学会総会・学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2008-08-23
• [Presentation] アデノシンによるNKT細胞、Gr-1+CD11b+細胞を介した移植早期膵島障害の制御 (2008)
  • Author(s): 新田智之, 松岡信秀, 伊東威, 米良利之, 中野昌彦, 山下裕一, 安波洋一
  • Organizer: 第108回日本外科学会定期学術集会
  • Place of Presentation: 長崎
  • Year and Date: 2008-05-16
• [Presentation] Adenosine has an inhibitory effect on NKT cells facilitating to prevent early loss of transplanted islets in association with engraftments (2008)
  • Author(s): T Nitta, N Matsuoka, T Itoh, T Mera, A Kinjo, M Nakano, Y Yamashita, Y Yasunami
  • Organizer: 22th International Congress of the Transplantation Society
  • Place of Presentation: Sydney, Australia
• [Presentation] Adenosine has an inhibitory effect on NKT cells facilitating to prevent early loss of transplanted islets in association with engraftments. (2008)
  • Author(s): T Nitta, N Matsuoka, T Itoh, T Mera, A Kinjo, M Nakano, Y Yamashita, Y Yasunami
  • Organizer: XXII International Congress of the Transplantation Society
  • Place of Presentation: Sydney, Australia
• [Presentation] Successful islet transplantation from one donor to one recipient by targeting IL-6/IL-6 receptor signaling in mice (2007)
  • Author(s): T Itoh, N Matsuoka, T Nitta, M Nakano, T Mera, Y Yamashita, J Ono, Y Yasunami
  • Organizer: Joint Conference of Cell Transplantation Society, International Pancreas and Islet transplant Association and Xenotransplantation Association
  • Place of Presentation: Minneapolis, USA
• [Presentation] Timing of the Second Grafts is Crucial in Sequential Islet Transplantations to Prevent Early Loss of Islets in the Liver of Mice in Relation to Induction of Hypo-responsiveness of NKT Cells (2007)
  • Author(s): N Matsuoka, T Itoh, T Nitta, M Nakano, K Anzai, J Ono, Y Yuichi Yamashita, M Taniguchi, Y Yasunami
  • Organizer: 67th Scientific Sessions of American Diabetes Association
  • Place of Presentation: Chicago, USA
• [Presentation] Timing of the Second Grafts is Crucial in Sequential Islet Trans plantations to Prevent Early Loss of Islets in the Liver of Mice in Relation to Induction of Hypo-responsiveness of NKT Cells (2007)
  • Author(s): N Matsuoka, T Itoh, T Nitta, M Nakano, K Anzai, J Ono, Y Yamashita, M Taniguchi, Y Yasunami
  • Organizer: 米国糖尿病学会
  • Place of Presentation: シカゴ(米国)
• [Presentation] Successfil islet transplantation from one donor to one recipient by targeting IL-6/1L-6 receptor signaling in mice (2007)
  • Author(s): T Itoh, N Matsuoka, T Nitta, M Nakano, T Mera, Y Yamashita, J Ono, Y Yasunami
  • Organizer: CTS, IPITA, IXA2007 Joint Conference
  • Place of Presentation: ミネアポリス(米国)
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2009)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2009-03-06
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2008)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2008-06-13
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2008)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2008-05-13
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2008)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2008-05-13
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2008)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2008-05-13
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2008)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2008-05-09
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2008)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2008-04-28
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2008)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2008-04-15
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2008)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2008-04-14
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2008)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2008-04-14
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2008)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2008-04-14
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2008)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2008-04-11
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2008)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2008-04-11
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2008)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2008-04-09
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2008)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2008-04-07
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2008)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2008-03-31
• [Patent(Industrial Property Rights)] 移植膵島障害に対する抗High Mobility Group Box 1(HMGB1)抗体の効果 (2008)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2008-02-15
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2007)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Industrial Property Number: 2007-539996
  • Filing Date: 2007-11-06
• [Patent(Industrial Property Rights)] 移植膵島障害に対する抗High Mobility Group Box 1(HMGB1)抗体の効果 (2007)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2007-02-15
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2006)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2006-10-28
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2006)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2006-10-13
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2006)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2006-10-13
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2006)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2006-10-13
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2006)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2006-10-13
• [Patent(Industrial Property Rights)] 膵島移植における移植膵島障害抑制剤 (2006)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2006-10-13
• [Patent(Industrial Property Rights)] 移植片喪失の予防剤、及びそのスクリーニング方法 (2006)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Filing Date: 2006-08-11