Role of natural killer T cells in chronic inflammation of atherogenesis

• Project/Area Number: 23591096
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Hokkaido University
• Principal Investigator: ISHIMORI Naoki 北海道大学, 大学病院, 准教授 (70399848)
• Co-Investigator(Kenkyū-buntansha): TSUTSUI Hiroyuki 北海道大学, 大学院医学研究科, 教授 (70264017) ; KINUGAWA Shintaro 北海道大学, 大学院医学研究科, 講師 (60399871)
• Research Collaborator: TOKUHARA Satoshi 北見赤十字病院, 循環器内科, 副部長 ; SAITO Akimichi 北海道大学, 大学病院, 医員 (40735502) ; NISHIKAWA Mikito 帯広協会病院, 循環器内科, 医長
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 慢性炎症 / 動脈硬化 / マクロファージ / リンパ球 / 免疫調節 / ナチュラルキラーＴ細胞 / 免疫応答 / 脂質異常症 / ナチュラルキラーT細胞

Outline of Final Research Achievements

The purpose of this study was to elucidate the role of natural killer T (NKT) cells in chronic inflammation elicited by dyslipidemia, which result in atherosclerosis. Splenocytes from apolipoprotein-E deficient mice, including mononuclear phagocytes and NKT cells, were cultured with α-Galactosylceramide (α-GalCer), which specifically activates NKT cells, and significantly reduced in the production of inflammatory cytokines compared to those from wild-type mice, suggesting NKT cell anergy. Splenocytes cultured with Th1 or Th2 cytokines were stimulated with α-GalCer, but did not differ in the production of inflammatory cytokines between apolipoprotein-E deficient mice and wild-type mice. Thus, we could not elucidate the significant role of NKT cells in chronic inflammation in the present study.

Research Products

• [Journal Article] AST-120 ameliorates lowered exercise capacity and mitochondrial biogenesis in the skeletal muscle from mice with chronic kidney disease via reducing oxidative stress. (2015)
  • Author(s): Nishikawa M, Ishimori N, Takada S, Saito A, Kadoguchi T, Furihata T, Fukushima A, Matsushima S, Yokota T, Kinugawa S, Tsutsui H
  • Journal Title: Nephrol Dial Transplant. Volume: in press Issue: 6 Pages: 182-188
  • DOI: 10.1093/ndt/gfv103
  • NAID: 120005743055
  • Peer Reviewed
• [Journal Article] Type II NKT cells stimulate diet-induced obesity by mediating adipose tissue inflammation, steatohepatitis and insulin resistance (2012)
  • Author(s): Satoh, M., Andoh, Y., Clingan, S. C., Ogura, H., Fujii, S., Nakayama, T., Taniguchi, M., Hirata, N., Ishimori, N., Tsutsui, H., Onoe, K. Iwabuchi, K
  • Journal Title: PLoS ONE Volume: 7(2) Issue: 2 Pages: 1-12
  • DOI: 10.1371/journal.pone.0030568
  • NAID: 120004043739
  • Peer Reviewed
• [Presentation] Circulating invariant natural killer T cells are decreased in patients with chronic heart failure. (2014)
  • Author(s): Saito A, Ishimori N, Nishikawa M, Kinugawa S, Tsutsui H
  • Organizer: American Heart Association Scientific Sessions 2014
  • Place of Presentation: McCormick Place （シカゴ・アメリカ）
  • Year and Date: 2014-11-17
• [Presentation] AST-120 ameliorates lowered exercise capacity and mitochondrial dysfunction of the skeletal muscle in mice with chronic kidney disease via reducing oxidative stress. (2014)
  • Author(s): Nishikawa M, Ishimori N, Takada S, Saito A, Kadoguchi T, Furihata T, Fukushima A, Matsushima S, Yokota T, Kinugawa S, Tsutsui H
  • Organizer: American Heart Association Scientific Sessions 2014
  • Place of Presentation: McCormick Place （シカゴ・アメリカ）
  • Year and Date: 2014-11-17
• [Presentation] Activation of invariant natural killer T cells ameliorates the development of angiotensin II-mediated abdominal aortic aneurysm formation in obese ob/ob mice. (2014)
  • Author(s): Saito A, Ishimori N, Tokuhara S, Nishikawa M, Tsutsui H
  • Organizer: European Society of Cardiology Congress 2014
  • Place of Presentation: Fira Gran Via （バルセロナ・スペイン）
  • Year and Date: 2014-09-01
• [Presentation] Activation of invariant natural killer T Cells ameliorates the development of angiotensin II-mediated abdominal aortic aneurysm formation in ob/ob mice. (2014)
  • Author(s): Saito A, Ishimori N, Tokuhara S, Nishikawa M, Tsutsui H
  • Organizer: The 18th International Vascular Biology Meeting
  • Place of Presentation: 京都市勧業館みやこめっせ（京都市）
  • Year and Date: 2014-04-15
• [Presentation] Natural killer T (NKT) cells are involved in the development of metabolic disorders and atherosclerosis. (2011)
  • Author(s): Ishimori N, Tokuhara S, Nozawa A, Saito A, Tsutsui H
  • Organizer: The 43rd Annual Scientific Meeting of the Japan Atherosclerosis Society
  • Place of Presentation: ロイトン札幌(北海道)
• [Presentation] Natural killer T cells are involved in aortic valvular calcification in uremic apolipoprotein-E deficient mice. (2011)
  • Author(s): Nozawa A, Ishimori N, Ohmura Y, Tokuhara S, Horii S, Saito A, Tsutsui H
  • Organizer: The 75th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: パシフィコ横浜(神奈川県)
• [Presentation] Natural killer T cells are differentially involved in the development of experimental aortic aneurysm in mice according to their subtypes. (2011)
  • Author(s): Tokuhara S, Ishimori N, Nozawa A, Saito A, Tsutsui H
  • Organizer: The 75th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: パシフィコ横浜(神奈川県)
• [Presentation] Natural killer T cells are involved in atherosclerotic plaque instability in apolipoprotein-E knockout mice. (2011)
  • Author(s): Ishimori N, Ohmura Y, Horii S, Tokuhara S, Nozawa A, Saito A, Tsutsui H
  • Organizer: European Society of Cardiology Congress
  • Place of Presentation: Parc des Expositions de Paris Nord Villepinte(France)
• [Presentation] Natural killer T Cells are involved in aortic valvular calcification in uremic apolipoprotein-E deficient mice. (2011)
  • Author(s): Nozawa A, Ishimori N, Ohmura Y, Tokuhara S, Saito A, Tsutsui H
  • Organizer: European Society of Cardiology Congress
  • Place of Presentation: Parc des Expositions de Paris Nord Villepinte(France)
• [Presentation] Natural killer T cells are involved in aortic valvular calcification via inhibiting osteoclastic differentiation in uremic apolipoprotein-E deficient mice. (2011)
  • Author(s): Ishimori N, Nozawa A, Tokuhara S, Saito A, Iwabuchi K, Tsutsui H
  • Organizer: The 6th International Symposium on CD1 and NKT Cells
  • Place of Presentation: University of Chicago Gleacher Center(America)
• [Presentation] Type II NKT cells operate diet-induced obesity by mediating adipose tissue inflammation, steatohepatitis and insulin resistance. (2011)
  • Author(s): Satoh M, Andoh Y, Clingan CS, Ogura H, Fujii S, Nakayama T, Taniguchi M, Ishimori N, Tsutsui H, Kaer LV, Onoé K, Iwabuchi K
  • Organizer: The 6th International Symposium on CD1 and NKT Cells
  • Place of Presentation: University of Chicago Gleacher Center(America)
• [Presentation] Natural killer T cells are involved in the development of experimental aortic aneurysm and dissection in apolipoprotein-E deficient mice. (2011)
  • Author(s): Tokuhara S, Ishimori N, Nozawa A, Saito A, Tsutsui H
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Orange County Convention Centre(America)
• [Presentation] Natural killer T cells are involved in aortic valvular calcification via inhibiting osteoclastic differentiation in uremic apolipoprotein-E deficient mice. (2011)
  • Author(s): Nozawa A, Ishimori N, Tokuhara S, Saito A, Tsutsui H
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Orange County Convention Centre(America)
• [Presentation] Type II NKT cells operate diet-induced obesity by mediating adipose tissue inflammation and steatohepatitis. (2011)
  • Author(s): Satoh M, Eshima K, Nakayama T, Taniguchi M, Ishimori N, Iwabuchi K
  • Organizer: The 40th Annual Scientific Meeting of the Japanese Society for Immunology
  • Place of Presentation: 幕張メッセ(千葉県)
• [Presentation] Natural killer T (NKT) cells are involved in the development of metabolic disorders and atherosclerotic diseases. (2011)
  • Author(s): Ishimori N, Tokuhara S, Nozawa A, Saito A, Tsutsui H
  • Organizer: The 28th Annual Meeting of the International Society for Heart Research Japanese Section
  • Place of Presentation: 学術総合センター(東京都)
• [Patent(Industrial Property Rights)] 樹状細胞を含有する医薬およびその製造方法 (2015)
  • Inventor(s): 筒井裕之・石森直樹・絹川真太郎・斎藤晶理
  • Industrial Property Rights Holder: 筒井裕之・石森直樹・絹川真太郎・斎藤晶理
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-02-26
  • Overseas