The novel function of adipocyte during activation of NKT cell in the obesity

• Project/Area Number: 16K21347
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics; Experimental pathology
• Research Institution: Kitasato University
• Principal Investigator: Satoh Masashi 北里大学, 医学部, 講師 (40611843)
• Research Collaborator: Iwabuchi Kazuya
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: NKT cell / Adipocyte / obesity / inflammation / insulin resistance / NKT細胞 / 脂肪細胞 / 脂肪組織炎症 / インスリン抵抗性 / 耐糖能異常 / 免疫学 / 細胞・組織 / 脂質

Outline of Final Research Achievements

We elucidated the interaction between NKT cell and adipocyte induced adipose tissue inflammation that aggravated glucose metabolism. These evidence were proved by using adipocyte-specific Cd1d deficient mice, that inhibit interaction between NKT cell and adipocyte via CD1d. However, the lipid ligands presented by adipocyte have not been cleared. If the ligands in adipocyte will be identified in the future, NKT cell might be a new theraputic target against obesity.

Academic Significance and Societal Importance of the Research Achievements

肥満に伴う臓器炎症は免疫細胞によって引き起こされ、その炎症は糖尿病や肥満に深く関わっている。本研究は、肥満炎症の誘導メカニズムとしてNKT細胞が重要であることを示した。本来、感染防御に働くNKT細胞が新たに代謝疾患との関連性もあることが示唆されたことは学術的にも意義があると考えている。また、糖代謝をコントロールする上で、NKT細胞をはじめとする免疫細胞の制御も重要であることが明らかとなり、新たな治療アプロ―チとして発展していくことを期待する。

Research Products

• [Journal Article] NKT細胞と脂肪組織 (2019)
  • Author(s): 岩渕 和也，佐藤 雅．
  • Journal Title: 生体の科学 Volume: 70 Pages: 130-134
• [Journal Article] Characterization of T cell receptors in a novel murine model of nickel-induced intraoral metal contact allergy. (2018)
  • Author(s): Nakasone Y, Kumagai K, Matsubara R, Shigematsu H, Kitaura K, Suzuki S, Satoh M, Hamada Y, and Suzuki R.
  • Journal Title: PLoS One Volume: 13 Issue: 12 Pages: e0209248-e0209248
  • DOI: 10.1371/journal.pone.0209248
  • Peer Reviewed / Open Access
• [Journal Article] Role of NKT cells in the development of obesity and insulin resistance: insights from recent progress. (2018)
  • Author(s): Satoh M, Iwabuchi K.
  • Journal Title: Front Immunol Volume: 9 Pages: 1314-1314
  • DOI: 10.3389/fimmu.2018.01314
  • Peer Reviewed / Open Access
• [Journal Article] Nerve growth factor regulation and production by macrophages in osteoarthritic synovium. (2017)
  • Author(s): Takano S, Uchida K, Inoue G, Miyagi M, Aikawa J, Iwase D, Iwabuchi K, Matsumoto T, Satoh M, Mukai M, Minatani A, Takaso M.
  • Journal Title: Clin Exp Immunol Volume: 190 Issue: 2 Pages: 235-243
  • DOI: 10.1111/cei.13007
  • Peer Reviewed / Open Access
• [Journal Article] A Novel Mouse Model of iNKT Cell-deficiency Generated by CRISPR/Cas9 Reveals a Pathogenic Role of iNKT Cells in Metabolic Disease. (2017)
  • Author(s): Ren Y, Sekine-Kondo E, Shibata R, Kato-Itoh M, Umino A, Yanagida A, Satoh M, Inoue K, Yamaguchi T, Mochida K, Nakae S, Van Kaer L, Iwabuchi K, Nakauchi H, Watarai H.
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 12765-12765
  • DOI: 10.1038/s41598-017-12475-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 脂肪組織におけるNKT細胞と脂肪細胞の相互作用 (2017)
  • Author(s): 佐藤 雅, 岩渕和也
  • Journal Title: 臨床免疫・アレルギー科 Volume: 68 Pages: 682-688
• [Journal Article] Invariant natural killer T cells play dual roles in the development of experimental autoimmune uveoretinitis. (2016)
  • Author(s): Satoh M, Namba K, Kitaichi N, Endo N, Kitamei H, Iwata D, Ohno S, Ishida S, Onoe K, Watarai H, Taniguchi M, Ishibashi T,
  • Journal Title: Exp Eye Res. Volume: 153 Pages: 79-89
  • DOI: 10.1016/j.exer.2016.10.003
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Communication between natural killer T cells and adipocytes. (2016)
  • Author(s): Satoh M, Iwabuchi K.
  • Journal Title: Adipocyte Volume: 5 Issue: 4 Pages: 389-393
  • DOI: 10.1080/21623945.2016.1241913
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] CRISPR/Cas9を用いたCD1d欠損胸腺腫細胞株の作製 (2016)
  • Author(s): 佐伯美帆、佐藤 雅、飯塚みさを、岩渕和也
  • Journal Title: 北里医学 Volume: 46 Pages: 49-51
  • NAID: 40020901267
  • Peer Reviewed
• [Journal Article] Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice. (2016)
  • Author(s): Satoh M, Hoshino M, Fujita K, Iizuka M, Fujii S, Clingan CS, Van Kaer L, Iwabuchi K.
  • Journal Title: Sci Rep Volume: 6 Issue: 1
  • DOI: 10.1038/srep28473
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Inhibitory function of NKT cells during early induction phase of nickel allergy. (2016)
  • Author(s): Hironori Okuno, Masashi Satoh, Emiko Takeuchi, Koji Eshima, Masazumi Terashima, Jun Komotori, Sonoko Habu, Hidekazu Tamauchi, Kazuya Iwabuchi.
  • Journal Title: Immunobiology Volume: in press Issue: 7 Pages: 833-838
  • DOI: 10.1016/j.imbio.2016.01.012
  • Peer Reviewed / Open Access
• [Journal Article] NKT細胞・NK細胞の脂肪細胞での役割 (2016)
  • Author(s): 佐藤 雅，岩渕和也
  • Journal Title: 医学のあゆみ Volume: 257 Pages: 681-685
  • Peer Reviewed
• [Presentation] NKT細胞による腸内細菌叢の制御 (2018)
  • Author(s): 佐藤 雅, 岩渕和也.
  • Organizer: 第７回ファージ研究会・ 2018年日本細菌学会 関東支部インターラボセミナー合同大会
• [Presentation] NKT cells control insulin sensitivity by interacting adipocytes and macrophages. (2018)
  • Author(s): Satoh M, Iwabuchi K.
  • Organizer: The 47th Annual Meeting of The Japanese Society for Immunology
• [Presentation] CD1d-positive antigen-presenting cells in the heart. (2018)
  • Author(s): Yoshino K, Satoh M, Iwabuchi K.
  • Organizer: The 47th Annual Meeting of The Japanese Society for Immunology
• [Presentation] The protective role of MR1/MAIT cell in allergic contact dermatitis. (2018)
  • Author(s): Imahashi N, Satoh M, Iwabuchi K.
  • Organizer: The 47th Annual Meeting of The Japanese Society for Immunology
• [Presentation] Modulation of NKT-cell function in mice fed on high fat diet (HFD) (2018)
  • Author(s): Hane K, Satoh M, Iwabuchi K.
  • Organizer: The 47th Annual Meeting of The Japanese Society for Immunology
• [Presentation] Amelioration of relapse model of experimental autoimmune uveoretinitis with NKT cell ligand. (2018)
  • Author(s): Kato T, Satoh M, Iwabuchi K.
  • Organizer: The 47th Annual Meeting of The Japanese Society for Immunology
• [Presentation] 新規NKT細胞ハイブリドーマの作製とその脂肪細胞との相互作用 (2017)
  • Author(s): 佐藤 雅, 岩渕和也
  • Organizer: 第28回日本生体防御学会学術総会
• [Presentation] NKT細胞による脂肪組織炎症・肥満の誘導 (2017)
  • Author(s): 佐藤 雅, 岩渕和也
  • Organizer: 第30回北里大学バイオサイエンスフォーラム
• [Presentation] Generation of CD1d-negative NKT-cell hybridomas (2017)
  • Author(s): Satoh M, Eshima K, Takeuchi E, Iizuka M, Iwabuchi K
  • Organizer: 第46回日本免疫学会学術集会
• [Presentation] NKT細胞-脂肪細胞の相互作用による脂肪組織炎症誘導メカニズム (2016)
  • Author(s): 佐藤 雅、岩渕 和也
  • Organizer: 第27回日本生体防御学会学術総会
  • Place of Presentation: 九州大学 病院キャンパス内 コラボステーションI 視聴覚ホール（福岡県福岡市）
• [Presentation] NKT cell - adipocyte interaction is necessary to induce adipose tissue inflammation (2016)
  • Author(s): Masashi Satoh, Koki Fujita, Misao Iizuka, Kazuya Iwabuchi
  • Organizer: 第45回日本免疫学会学術集会
  • Place of Presentation: 沖縄コンベンションセンター、ラグナガーデンホテル（沖縄県宜野湾市）
• [Remarks] 北里大学医学部免疫学ホームページ
  • URL: http://www.med.kitasato-u.ac.jp/immunology/
• [Remarks] 北里大学医学部免疫学ホームページ
  • URL: http://www.med.kitasato-u.ac.jp/immunology/index.html