Role of innate lymphoid cells in adipose tissue homeostasis

• Project/Area Number: 16H02631
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Koyasu Shigeo 国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (90153684)
• Co-Investigator(Kenkyū-buntansha): 茂呂 和世 国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (90468489)
• Research Collaborator: Sasaki Takaharu ; Ealey Kafi N.
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥43,680,000 (Direct Cost: ¥33,600,000、Indirect Cost: ¥10,080,000); Fiscal Year 2018: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000); Fiscal Year 2017: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000); Fiscal Year 2016: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
• Keywords: 肥満 / 自然リンパ球 / 脂肪組織炎症 / 炎症 / 脂肪組織 / 免疫学

Outline of Final Research Achievements

Using Rag2-/- mice lacking adaptive immune cells and γc-/-Rag2-/- mice lacking all lymphocytes, we have revealed that group 2 innate lymphoid cells (ILC2) and group 3 innate lymphoid cells (ILC3) from small intestine (SI-ILC2 and SI-ILC3, respectively) and IL-2 derived from those SI-ILCs are involved in the diet-induced obesity. Contrary to SI-ILC2, ILC2 derived from white adipose tissue (WAT-ILC2) suppressed adipocyte differentiation in an in vitro culture system, indicating that SI-ILC2 and WAT-ILC2 have different functions.

Academic Significance and Societal Importance of the Research Achievements

肥満は様々な生活習慣病の背景となることから、社会的な問題となっている。我々の研究は過去10年の間にその存在が明らかにされた、抗原受容体を持たないリンパ球である自然リンパ球が肥満の誘導に関わることを明らかにした。さらに、寄生虫に対する感染防御やアレルギー性炎症に関係すると考えられてきた2型自然リンパ球（ILC2）が腸管と脂肪組織において異なる性質を持つこと、すなわち、腸管のILC2は肥満を誘導するのに対し、脂肪組織のILC2が脂肪細胞の分化を抑制する点は興味深い。今後これらの活性の分子機構の詳細を明らかにすることで肥満の予防や治療に繋がる新たな発見が期待される。

Research Products

• [Int'l Joint Research] University of Bergen(ノルウェー)
• [Int'l Joint Research] Cornell University/Washington University/University of California San Francisco(米国)
• [Int'l Joint Research] MRC Laboratory of Molecular Biology/University of Oxford(英国)
• [Int'l Joint Research] CIML/Institut Pasteur(フランス)
• [Int'l Joint Research] Berlin Institute of Health(ドイツ)
• [Int'l Joint Research]
• [Journal Article] Innate lymphoid cells in the induction of obesity. (2019)
  • Author(s): Sasaki, T., Moro, K., Kubota, T., Kubota, N., Kato, T., Ohno, H., Nakae, S., Saito, H. and Koyasu, S.
  • Journal Title: Cell Reports Volume: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] Hide and seek: Plasticity of innate lymphoid cells in cancer. (2019)
  • Author(s): Bald, T., Wagner, M., Gao, Y., Koyasu, S. and Smyth, M. J.
  • Journal Title: Seminars in Immunology Volume: 印刷中 Pages: 101273-101273
  • DOI: 10.1016/j.smim.2019.04.001
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Cancer immunoediting by innate lymphoid cells. (2019)
  • Author(s): Wagner, M. and Koyasu, S.
  • Journal Title: Trends in Immunology Volume: 40 Issue: 5 Pages: 415-430
  • DOI: 10.1016/j.it.2019.03.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The group 2 innate lymphoid cell (ILC2) regulatory network and its underlying mechanisms (2018)
  • Author(s): Kabata Hiroki、Moro Kazuyo、Koyasu Shigeo
  • Journal Title: Immunological Reviews Volume: 286 Issue: 1 Pages: 37-52
  • DOI: 10.1111/imr.12706
  • Peer Reviewed
• [Journal Article] Innate lymphoid cells: 10 years on. (2018)
  • Author(s): Vivier, E., Artis, D., Colonna, M., Diefenbach, A., Di Santo, J. P., Eberl, G., Koyasu, S., Locksley, R. M., McKenzie, A. N. J., Mebius, R. E., Powrie, F. and Spits, H.
  • Journal Title: Cell Volume: 174 Issue: 5 Pages: 1054-1066
  • DOI: 10.1016/j.cell.2018.07.017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Peripheral PDGFRα+gp38+ mesenchymal cells support the differentiation of fetal liver-derived ILC2. (2018)
  • Author(s): Koga, S., Hozumi, K., Hirano, K.I., Yazawa, M., Terooatea, T., Minoda, A., Nagasawa, T., Koyasu, S., and Moro, K.
  • Journal Title: J Exp Med. Volume: 215 Issue: 6 Pages: 1609-1626
  • DOI: 10.1084/jem.20172310
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Plastic heterogeneity of innate lymphoid cells in cancer. (2017)
  • Author(s): Wagner, M., Moro, K. and Koyasu, S.
  • Journal Title: Trends in Cancer Volume: 5 Issue: 5 Pages: 326-335
  • DOI: 10.1016/j.trecan.2017.03.008
  • Peer Reviewed
• [Journal Article] Are ILC2s Jekyll and Hyde in airway inflammation? (2017)
  • Author(s): Ealey, K. N., Moro, K. and Koyasu, S.
  • Journal Title: Immunological Reviews Volume: 278 Issue: 1 Pages: 207-218
  • DOI: 10.1111/imr.12547
  • Peer Reviewed
• [Journal Article] Innate lymphoid cells in allergic and nonallergic inflammation. (2016)
  • Author(s): Morita H, Moro K, Koyasu S.
  • Journal Title: J Allergy Clin Immunol. Volume: 138(5) Issue: 5 Pages: 1253-1264
  • DOI: 10.1016/j.jaci.2016.09.011
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Tolerance break by class switch recombination for auto-antibody production. (2018)
  • Author(s): Shigeo Koyasu
  • Organizer: The 7th FIMSA Congress
  • Int'l Joint Research / Invited
• [Presentation] Environmental factors controlling the peripheral differentiation of ILC2. (2018)
  • Author(s): Shigeo Koyasu
  • Organizer: The 32nd Collegium Internationale Allergologicum
  • Int'l Joint Research
• [Presentation] Innate lymphoid cells, a new type of lymphocytes without antigen receptors. (2018)
  • Author(s): Shigeo Koyasu
  • Organizer: Interdiscipilinary Science Conference
  • Int'l Joint Research / Invited
• [Presentation] Involvement of innate lymphoid cells in the iduction of diet-induced obesity. (2018)
  • Author(s): Takaharu Sasaki, Kazuyo Moro, Tetsuya Kubota, Naoto Kubota, Hiroshi Ohno, Shigeo Koyasu
  • Organizer: The 3rd International Conference on Innate Lymphoid Cells
  • Int'l Joint Research
• [Presentation] Mechanisms for the regulation of adipose tissue expansion and remodeling by group 2 innate lymphoid cells. (2018)
  • Author(s): Kafi Nequan Ealey, Shigeo Koyasu, Yibo Wu, Kazuyo Moro
  • Organizer: The 3rd International Conference on Innate Lymphoid Cells
  • Int'l Joint Research
• [Presentation] Group 2 innate lymphoid cells regulate susceptibility to allergic lung inflammation via an innate amplification circuit. (2018)
  • Author(s): Yasutaka Motomura, Shigeo Koyasu, Kazuyo Moro
  • Organizer: The 3rd International Conference on Innate Lymphoid Cells
  • Int'l Joint Research
• [Presentation] Group 2 innate lymphoid cells exacerbate severe amebic liver abscess by IFN-gamma independent manner in mice. (2018)
  • Author(s): Risa Nakamura, Sharmina Deloer, Masachika Senba, Mihoko Kikuchi, Shigeo Koyasu, Kazuyo Moro, Shinjiro Hamano
  • Organizer: The 3rd International Conference on Innate Lymphoid Cells
  • Int'l Joint Research
• [Presentation] Innate lymphoid cells in helminth infection (2017)
  • Author(s): Shigeo Koyasu
  • Organizer: The 10th Congress of the Federation of African Immunological Societies
  • Int'l Joint Research / Invited
• [Presentation] IL-7 and Notch conditionally control the commitment of ILC2 differentiation. (2016)
  • Author(s): Shigeo Koyasu
  • Organizer: 2nd EMBO Conference “Innate lymphoid cells”
  • Place of Presentation: Kalkscheune, Berlin, Germany
  • Year and Date: 2016-12-02
  • Int'l Joint Research / Invited
• [Presentation] Regulatory mechanisms for ILC2 activation in allergic inflammation. (2016)
  • Author(s): Shigeo Koyasu
  • Organizer: 4th Annual Meeting of the International Cytokine and Interferon Society
  • Place of Presentation: Hyatt Regency San Francisco, San Francisco, CA, USA
  • Year and Date: 2016-10-19
  • Int'l Joint Research / Invited
• [Presentation] Regulatory mechanisms for ILC2 functions in allergic inflammation. (2016)
  • Author(s): Shigeo Koyasu, Hiroki Kabata, Satoshi Koga, Kazuyo Moro
  • Organizer: 16th International Congress of Immunology
  • Place of Presentation: Melbourne Convention and Exhibition Centre, Melbourne, Australia
  • Year and Date: 2016-08-22
  • Int'l Joint Research / Invited
• [Remarks] 理化学研究所 生命医科学研究センター 免疫細胞システム研究チーム
  • URL: http://www.ims.riken.jp/labo/43/index_j.html
• [Remarks] 理化学研究所 生命医科学研究センター 免疫細胞システム研究チーム
  • URL: http://www.riken.jp/research/labs/ims/immun_cell_sys/
• [Remarks] 理化学研究所 統合生命医科学研究センター 免疫細胞システム研究グループ
  • URL: http://www.riken.jp/research/labs/ims/immun_cell_sys/
• [Remarks] 理化学研究所 統合生命医科学研究センター 免疫細胞システム研究グループ
  • URL: http://www.ims.riken.jp/labo/43/index_j.html