Role of natural helper cells in adipose tissue inflammation

• Project/Area Number: 25670235
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: KOYASU Shigeo 独立行政法人理化学研究所, 統合生命医科学研究センター, センター長 (90153684)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: マクロファージ / 腸管 / 粘膜固有層 / 自然リンパ球 / IL-7 / 肥満 / 自然免疫 / リンパ球 / 脂肪細胞 / 好酸球

Outline of Final Research Achievements

γc-/-Rag2-/- mice deficient for all lymphocytes were resistant to high-fat diet (HFD)-induced obesity. Adoptive transfer of NH cells derived from small intestinal lamina propria (LP) but not those from mesentery restored weight gain of γc-/-Rag2-/- mice upon HFD. Co-cultivation of macrophage with NH cells in vitro increased anti-inflammatory M1 macrophages as expected. On the other hand, adoptive transfer of LP NH cells into γc-/-Rag2-/- mice resulted in the increase of pro-inflammatory M1 macrophages as well as eosinophils in adipose tissues in vivo. These results suggest that NH cells are involved in HFD-induced obesity and adipose tissue inflammation through mechanisms distinct from type 2 cytokine-mediated pathway.

Research Products

• [Journal Article] Isolation and analysis of group 2 innate lymphoid cells in mice. (2015)
  • Author(s): Moro K, Ealey KN, Kabata H, Koyasu S
  • Journal Title: Nat Protoc. Volume: 10 Issue: 5 Pages: 792-806
  • DOI: 10.1038/nprot.2015.047
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue-resident regulatory T cells. (2015)
  • Author(s): Vasanthakumar A, Moro K, Xin A, Liao Y, Gloury R, Kawamoto S, Fagarasan S, Mielke LA, Afshar-Sterle S, Masters SL, Nakae S, Saito H, Wentworth JM, Li P, Liao W, Leonard WJ, Smyth GK, Shi W, Nutt SL, Koyasu S, Kallies A
  • Journal Title: Nat Immunol. Volume: 16 Issue: 3 Pages: 276-285
  • DOI: 10.1038/ni.3085
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Inflammatory ILC2 cells: disguising themselves as progenitors? (2015)
  • Author(s): Koyasu S
  • Journal Title: Nat Immunol. Volume: 16 Issue: 2 Pages: 133-134
  • DOI: 10.1038/ni.3080
• [Journal Article] Innate lymphoid cells, possible interaction with microbiota. (2015)
  • Author(s): Moro K, Koyasu S
  • Journal Title: Semin Immunopathol. Volume: 37 Issue: 1 Pages: 27-37
  • DOI: 10.1007/s00281-014-0470-4
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Development, differentiation, and diversity of innate lymphoid cells (2014)
  • Author(s): Diefenbach A, Colonna M, Koyasu S
  • Journal Title: Immunity Volume: 41 Issue: 3 Pages: 354-365
  • DOI: 10.1016/j.immuni.2014.09.005
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A novel mouse model of soft-tissue infection using bioluminescence imaging allows noninvasive, real-time monitoring of bacterial growth. (2014)
  • Author(s): Yoshioka K, Ishii K, Kuramoto T, Nagai S, Funao H, Ishihama H, Shiono Y, Sasaki A, Aizawa M, Okada Y, Koyasu S, Toyama Y, Matsumoto M
  • Journal Title: PLoS One Volume: 9 Issue: 9 Pages: e106367-e106367
  • DOI: 10.1371/journal.pone.0106367
  • Peer Reviewed / Open Access
• [Journal Article] Basophil-derived interleukin-4 controls the function of natural helper cells, a member of ILC2s, in lung inflammation. (2014)
  • Author(s): Motomura Y, Morita H, Moro K, Nakae S, Artis D, Endo TA, Kuroki Y, Ohara O, Koyasu S, Kubo M
  • Journal Title: Immunity Volume: 40 Issue: 5 Pages: 758-771
  • DOI: 10.1016/j.immuni.2014.04.013
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Phagocytic cells contribute to the antibody-mediated elimination of pulmonary-infected SARS coronavirus. (2014)
  • Author(s): Yasui F, Kohara M, Kitabatake M, Nishiwaki T, Fujii H, Tateno C, Yoneda M, Morita K, Matsushima K, Koyasu S, Kai C
  • Journal Title: Virology Volume: 454-455 Pages: 157-168
  • DOI: 10.1016/j.virol.2014.02.005
  • Peer Reviewed / Open Access
• [Journal Article] Th2-type innate immune responses mediated by natural helper cells. (2013)
  • Author(s): Koyasu S, Moro K.
  • Journal Title: Ann N Y Acad Sci. Volume: 1283 Issue: 1 Pages: 43-9
  • DOI: 10.1111/nyas.12106
  • Peer Reviewed
• [Journal Article] Critical role of p38 and GATA3 in natural helper cell function. (2013)
  • Author(s): Furusawa J, Moro K, Motomura Y, Okamoto K, Zhu J, Takayanagi H, Kubo M, Koyasu S.
  • Journal Title: J Immunol. Volume: 191 Issue: 4 Pages: 1818-26
  • DOI: 10.4049/jimmunol.1300379
  • Peer Reviewed
• [Journal Article] Critical role of p38 and GATA3 in natural helper cell function. (2013)
  • Author(s): Kabata H, Moro K, Fukunaga K, Suzuki Y, Miyata J, Masaki K, Betsuyaku T, Koyasu S, Asano K.
  • Journal Title: Nat Commun. Volume: 4 Issue: 1 Pages: 2675-2675
  • DOI: 10.1038/ncomms3675
  • Peer Reviewed
• [Journal Article] The prostaglandin E2 receptor EP4 is involved in a positive feedback loop for prostaglandin E2 production in human macrophages infected with Mycobacterium tuberculosis. (2013)
  • Author(s): Nishimura T., Zhao X., Gan H., Koyasu S., Remold HG.
  • Journal Title: FASEB J Volume: 27 Issue: 9 Pages: 3827-3836
  • DOI: 10.1096/fj.13-228858
  • Peer Reviewed
• [Journal Article] proteomic approach for the elucidation of stimulus- and substrate-specificity of ectodomain shedding. (2013)
  • Author(s): Shirakabe K., Shibagaki Y., Yoshimura A., Koyasu S., Hattori S.
  • Journal Title: J Proteomics Volume: 98 Pages: 233-243
  • DOI: 10.1016/j.jprot.2014.01.012
  • Peer Reviewed / Open Access
• [Presentation] 寄生虫感染における2型自然リンパ球「ナチュラルヘルパー細胞」の役割 (2015)
  • Author(s): 小安重夫，茂呂和世
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 三鷹、杏林大学三鷹キャンパス
  • Year and Date: 2015-03-22
  • Invited
• [Presentation] Group 2 innate lymphoid cells and allergic inflammation (2015)
  • Author(s): Shigeo Koyasu
  • Organizer: The 9th World Immune Regulation Meeting
  • Place of Presentation: Davos, Switzerland
  • Year and Date: 2015-03-19
  • Invited
• [Presentation] Role of Natural Helper cells, a member of group 2 ILCs, in obesity. (2014)
  • Author(s): Takaharu Sasaki, Kazuyo Moro, Shigeo Koyasu
  • Organizer: The 43rd Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: 京都、国立京都国際会館
  • Year and Date: 2014-12-12
• [Presentation] Innate lymphoid cells and inflammation (2014)
  • Author(s): Kazuyo Moro, Shigeo Koyasu
  • Organizer: The 43rd Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: 京都、国立京都国際会館
  • Year and Date: 2014-12-11
  • Invited
• [Presentation] Critical role of IL-7 and Notch signaling in natural helper cell development. (2014)
  • Author(s): Satoshi Koga, Kazuyo Moro, Shigeo Koyasu
  • Organizer: The 43rd Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: 京都、国立京都国際会館
  • Year and Date: 2014-12-10
• [Presentation] Role of natural helper cells, a member of group 2 innate lymphoid cells (ILC2), in allergic inflammation (2014)
  • Author(s): Shigeo Koyasu
  • Organizer: The 24th Hot Spring Harbor International Symposium “Recent Advances in Immunology and Inflammation 2014”
  • Place of Presentation: 福岡、九州大学病院キャンパスコラボステーション
  • Year and Date: 2014-11-08
  • Invited
• [Presentation] Role of natural helper cells, a member of group 2 innate lymphoid cells (ILC2s), in allergic inflammation (2014)
  • Author(s): Shigeo Koyasu
  • Organizer: 2014 NHRI/IBMS Joint International Conference on Inflammation & Disease
  • Place of Presentation: Ｔａｉｐｅｉ，Ｔａｉｗａｎ
  • Year and Date: 2014-10-18
  • Invited
• [Presentation] 寄生虫感染防御に対する自然免疫反応とナチュラルヘルパー細胞 (2014)
  • Author(s): 小安重夫，田邉将信，茂呂和世
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都、国立京都国際会館
  • Year and Date: 2014-10-16
  • Invited
• [Presentation] The role of basophils in the activation of lung ILC2 in allergic inflammation in the lung. (2014)
  • Author(s): Shigeo Koyasu, Yasutaka Motomura, Kazuyo Moro
  • Organizer: EMBO Conference on Innate Lymphoid Cells 2014
  • Place of Presentation: Paris, France
  • Year and Date: 2014-10-01
  • Invited
• [Presentation] Role of Natural Helper Cells, a member of group 2 innate lymphoid cells (ILC2s), in health and diseases. (2014)
  • Author(s): Shigeo Koyasu, Kazuyo Moro
  • Organizer: Cold Spring Harbor Asia Conferences “Frontiers of Immunology in Health and Diseases”
  • Place of Presentation: Suzhou, China
  • Year and Date: 2014-09-02
  • Invited
• [Presentation] Involvement of natural helper cells in the onset of diet-induced obesity. (2014)
  • Author(s): Takaharu Sasaki, Kazuyo Moro, Tetsuya Kubota, Naoto Kubota, Takashi Kadowaki, Shigeo Koyasu
  • Organizer: The 22nd International Symposium on Molecular Cell Biology of Macrophages “Macrophage in Maintenance of Tissue Homeostasis and Diseases”
  • Place of Presentation: 神戸、神戸商工会議所
  • Year and Date: 2014-06-02
• [Presentation] システインプロエアーゼによって誘導される肺のアレルギー炎症における好塩基球由来のIL-4の役割 (2014)
  • Author(s): 本村泰隆，森田英明，茂呂和世，中江進，遠藤高帆，黒木陽子，小原収，小安重夫，久保允人
  • Organizer: Kyoto T Cell Conference 第24回学術集会
  • Place of Presentation: 京都、京都平安ホテル
  • Year and Date: 2014-05-17
• [Presentation] ナチュラルヘルパー細胞の分化機構解明 (2014)
  • Author(s): 古賀諭，茂呂和世，小安重夫
  • Organizer: Kyoto T Cell Conference 第24回学術集会
  • Place of Presentation: 京都、京都平安ホテル
  • Year and Date: 2014-05-17
• [Presentation] アレルギー性炎症と自然リンパ球 (2014)
  • Author(s): 小安重夫
  • Organizer: 第26回日本アレルギー学会春季臨床大会
  • Place of Presentation: 京都、国立京都国際会館
  • Year and Date: 2014-05-11
  • Invited
• [Presentation] 重症喘息におけるナチュラルヘルパー細胞の関与と治療法の探索 (2014)
  • Author(s): 加畑宏樹，茂呂和世，小安重夫，浅野浩一郎
  • Organizer: 第26回日本アレルギー学会春季臨床大会
  • Place of Presentation: 京都、国立京都国際会館
  • Year and Date: 2014-05-09
• [Presentation] Role of natural helper cell, a member for the ILC (ILC2) in steroid resistance of allergic inflammation.
  • Author(s): Shigeo Koyasu
  • Organizer: Keystone Symposia “Advances in the Knowledge and Treatment of Autoimmunity”
  • Place of Presentation: British Columbia, Canada
  • Invited
• [Presentation] Natural helper cells and type-2 innate immune responses
  • Author(s): Shigeo Koyasu
  • Organizer: 5th Symposium & Master Classes on Mucosal Immunology: “Cytokines and border patrol”
  • Place of Presentation: Rotterdam, Kingdom of Netherlands
  • Invited
• [Presentation] Allergic inflammation and a newly identified innate lymphocyte, natural helper (NH) cell.
  • Author(s): Shigeo Koyasu
  • Organizer: The 3rd McGill-RIKEN Workshop on Advanced Biomedical Sciences
  • Place of Presentation: Montreal, Canada
• [Presentation] Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells in the inflamed airways.
  • Author(s): Shigeo Koyasu
  • Organizer: 6th International Conference on Autoimmunity: Mechanism and Novel Treatments
  • Place of Presentation: Corfu, Greece
  • Invited
• [Presentation] Role of natural helper cells, a member of group 2 innate lymphoid cells, in helminth infection
  • Author(s): Shigeo Koyasu
  • Organizer: RIKEN RCAI International Summer Program 2013
  • Place of Presentation: Yokohama
• [Presentation] アレルギー性炎症とナチュラルヘルパー細胞
  • Author(s): 小安 重夫
  • Organizer: 第45回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 自然リンパ球
  • Author(s): 小安 重夫
  • Organizer: 第41回日本臨床免疫学会総会
  • Place of Presentation: 下関
  • Invited
• [Presentation] Role of natural helper cells in obesity
  • Author(s): Takaharu Sasaki, Kazuyo Moro, Shigeo Koyasu
  • Organizer: Annunal Meeting of the Japanese Society for Immunology, 2013
  • Place of Presentation: Makuhari
• [Presentation] Critical role of basophil derived IL-4 in natural helper cell-mediated lung inflammation
  • Author(s): Yasutaka Motomura, Kazuyo Moro, Hideaki Morita, Susumu Nakae, Shigeo Koyasu, Masato Kubo
  • Organizer: Annunal Meeting of the Japanese Society for Immunology, 2013
  • Place of Presentation: Makuhari
• [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/