Functional study of IL-5-producing cells in food allergy using GFP marking system

• Project/Area Number: 24580196
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Food science
• Research Institution: Dokkyo Medical University
• Principal Investigator: MASAAKI Hashiguchi 獨協医科大学, 医学部, 准教授 (20372443)
• Research Collaborator: KOBAYASHI Ayano
• Project Period (FY): 2012-04-01 – 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 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: アレルギー / IL-5 / IL-33 / 好酸球 / GFP / マーキング

Outline of Final Research Achievements

Eosinophils are multifunctional leukocytes involved in parasite elimination, evocation of allergic reactions, and regulation of adipose tissue. IL-5 is required for eosinophil survival; however, the in vivo mechanisms of eosinophil regulation are not fully understood. A transgenic (tg) mouse model with Il5 promoter-driven EGFP expression was established for detecting the IL-5-producing cells in vivo. The first part of the results demonstrate that innate lymphoid cells (ILCs) activate eosinophils in GAT. The blockage of IL-33R, on the other hand, did not impair EGFP+ ILC numbers but did impair eosinophil numbers in vivo. IL-33 was found to expand eosinophil numbers in CD90+ cell-depleted mice. The latter part of findings demonstrate that IL-33 directly activates eosinophils in GAT, and together with our other findings described above, our findings show that IL-33 has dual pathways via which it activates eosinophils in vivo: a direct activation pathway and a group 2 ILC-mediated pathway.

Research Products

• [Journal Article] IL-33 activates eosinophils of visceral adipose tissue both directly and via innate lymphoid cells (2015)
  • Author(s): Hashiguchi, M., Kashiwakura, Y., Kojima, H., Kobayashi, A., Kanno, Y., Kobata, T.
  • Journal Title: Eur. J. Immunol. Volume: 45 Issue: 3 Pages: 876-885
  • DOI: 10.1002/eji.201444969
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Dual activation pathways of visceral adipose tissue eosinophils by interleukin-33 in vivo: innate lymphoid cell-mediated and direct actions (2014)
  • Author(s): Hashiguchi Masaaki, Kashiwakura Yuji, Kojima Hidefumi, Kanno Yumiko, Kobata Tetsuji
  • Organizer: 日本免疫学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-11
• [Presentation] IL-5 is produced by a novel subset of innate lymphoid cell with phenotypes of Lin^- Thy1.2^low-int CD25^+ IL-33Rα^+ in Peyer’s patches
  • Author(s): Masaaki Hashiguchi, Yuji Kashiwakura, Yumiko Kanno, Hidefumi Kojima, Tetsuji Kobata
  • Organizer: 日本免疫学会学術集会
  • Place of Presentation: 幕張
• [Presentation] NF-κB downregulates IL-5 production via upregulation of T-box proteins
  • Author(s): Masaaki Hashiguchi, Hidefumi Kojima, Yuji Kashiwakura, Yumiko Kanno, Tetsuji Kobata
  • Organizer: 日本免疫学会学術集会
  • Place of Presentation: 神戸