Clarification of the interaction between adipocyte and NKT cell and its application to metabolic syndrom

• Project/Area Number: 25870708
• 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, 助教 (40611843)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: NKT細胞 / 脂肪細胞 / 脂肪組織炎症 / メタボリックシンドローム / 抗原提示 / 炎症 / インスリン抵抗性 / 肥満 / メタボリック症候群 / 脂肪組織 / サイトカイン

Outline of Final Research Achievements

To examine the interaction between adipocyte and NKT cell, NKT cells were cultured with differentiated 3T3-L1 adipocytes. We found that 3T3-L1 adipocytes expressed CD1d and presented the endogenous ligand to NKT cells. Activated NKT cells produced cytokines including IFN-g. Furthermore, IFN-g acted on adipocytes to induce more the expression of Cd1d1 and downregulated the expression of Adipoq. It was suggested that NKT cells have a pathogenic role to induce adipose tissue inflammation and insulin resistance by interacting with adipocytes.

Research Products

• [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] Synovial macrophage-derived IL-1b regulates the calcitonin receptor in osteoarthritic mice. (2016)
  • Author(s): Takano S, Uchida K, Miyagi M, Inoue G, Aikawa J, Fujimaki H, Minatani A, Sato M, Iwabuchi K, Takaso M.
  • Journal Title: Clin Exp Immunol Volume: 183 Issue: 1 Pages: 143-149
  • DOI: 10.1111/cei.12712
  • Peer Reviewed
• [Journal Article] NKT細胞標的療法の新展開．代謝性疾患とNKT細胞 (2015)
  • Author(s): 佐藤 雅，岩渕和也
  • Journal Title: 医学のあゆみ Volume: 254 Pages: 1169-1174
• [Journal Article] Differential dependence on nuclear factor-κB-inducing kinase among natural killer T-cell subsets in their development. (2015)
  • Author(s): Noma H, Eshima K, Satoh M, Iwabuchi K
  • Journal Title: Immunology Volume: 146 Issue: 1 Pages: 89-99
  • DOI: 10.1111/imm.12484
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] CD11c+ macrophages and levels of TNF-α and MMP-3 are increased in synovial and adipose tissues of osteoarthritic mice with hyperlipidemia. (2015)
  • Author(s): Uchida K, Satoh M, Inoue G, Onuma K, Miyagi M, Iwabuchi K, Takaso M.
  • Journal Title: Exp Clin Immunol Volume: in press Issue: 3 Pages: 551-559
  • DOI: 10.1111/cei.12607
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Amelioration of experimental autoimmune uveoretinitis by inhibition of glyceraldehyde derived-advanced glycation end product formation. (2014)
  • Author(s): Dong Z, Iwata D, Kitaichi N, Takeuchi M, Sato M, Endo N, Iwabuchi K, Ando R, Fukuhara J, Kinoshita S, Lennikov A, Kitamura M, Mizuuchi K, Kanda A, Noda K, Namba K, Yamagishi S, Ohno S, Ishida S
  • Journal Title: J Leukoc Biol Volume: 96 Issue: 6 Pages: 1077-1085
  • DOI: 10.1189/jlb.3a0513-288rrr
  • Peer Reviewed / Open Access
• [Journal Article] TNF-α production in NKT cell hybridoma is regulated by sphingosine-1-phosphate: Ramifications of correlation between plasma S1P levels and metabolic syndrome (2014)
  • Author(s): Shiori Ito
  • Journal Title: Coron. Artery Dis. Volume: 25 Issue: 4 Pages: 311-320
  • DOI: 10.1097/mca.0000000000000082
  • Peer Reviewed
• [Journal Article] Increase of circulating CD11b+ Gr1+ cells and recruitment into synovium in osteoarthritis mice with hyperlipidemia. (2013)
  • Author(s): Uchida K, Naruse K, Satoh M, Onuma K, Ueno M, Takano S, Urabe K, Takaso M
  • Journal Title: Experimental Animals Volume: 62 Pages: 255-265
  • Peer Reviewed
• [Journal Article] Invariant NKT cell serves as a novel therapeutic target for control of obesity. (2013)
  • Author(s): Iwabuchi K, Satoh M
  • Journal Title: Clicical Lipidology Volume: 8 Issue: 1 Pages: 51-54
  • DOI: 10.2217/clp.12.83
  • Peer Reviewed
• [Journal Article] Natural killer T cells are required for lipopolysaccharide-mediated enhancement of atherosclerosis in apolipoprotein E-deficient mice (2013)
  • Author(s): Andoh Y, Ogura H, Satoh M, Shimano K, Okuno H, Fujii S, Ishimori N, Eshima K, Tamauchi H, Otani T, Nakai Y, Van Kaer L, Tsutsui H, Onoe K, Iwabuchi K
  • Journal Title: Immunobiology Volume: 218 Issue: 4 Pages: 561-569
  • DOI: 10.1016/j.imbio.2012.07.022
  • Peer Reviewed
• [Journal Article] 内臓脂肪症候群とNKT細胞 -NKT細胞による食餌誘導性肥満の促進 (2013)
  • Author(s): 佐藤 雅、岩渕 和也
  • Journal Title: 医学のあゆみ Volume: 246 Pages: 215-220
• [Presentation] NKT cell-adipocyte interaction modulate adipose tissue function (2015)
  • Author(s): Masashi Satoh and Kazuya Iwabuchi
  • Organizer: CD1-MR1 2015
  • Place of Presentation: ローン（オーストラリア）
  • Year and Date: 2015-11-14
  • Int'l Joint Research
• [Presentation] Adipocytes activate NKT cells via CD1d (2014)
  • Author(s): Masashi Satoh, Koji Eshima, Emiko Takeuchi, Kazuya Iwabuchi
  • Organizer: 第４３回 日本免疫学会学術集会
  • Place of Presentation: 京都国際会議場(京都府京都市)
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Characterization of non-invariant NKT cells in visceral adipose tissue
  • Author(s): Masashi Satoh, Koji Eshima, Emiko Takeuchi, Kazuya Iwabuchi
  • Organizer: 第４２回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ、千葉
• [Presentation] Characterization of non-invariant NKT cells in visceral adipose tissue
  • Author(s): Masashi Satoh, Koji Eshima, Emiko Takeuchi, Kazuya Iwabuchi
  • Organizer: ７th THE INTERNATIONAL SYNPOSIUM ON CD1 AND NKT CELLS
  • Place of Presentation: Tours, France
• [Presentation] The preventive effect of a novel ligand for natural killer T cells in the development of experimental autoimmune uveoretinitis in mice
  • Author(s): Masashi Satoh; Ken-ichi Namba; Nobuyoshi Kitaichi; Masaru Taniguchi; Luc Van Kaer; Koh-Hei Sonoda; Kazuya Iwabuchi
  • Organizer: The 6th International Workshop of Kyoto T Cell Conference
  • Place of Presentation: 京都大学医学部創立百周年記念施設 芝蘭会館、京都
• [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
• [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/