Research for signaling molecules that regulate mast cell-mediated allergic reactions

• Project/Area Number: 17K00907
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Eating habits
• Research Institution: National Institute of Health Sciences
• Principal Investigator: Tamehiro Norimasa 国立医薬品食品衛生研究所, 生化学部, 協力研究員 (80597881)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: マスト細胞 / IgE / 食物アレルギー / 脱顆粒 / 食品機能性分子 / アレルギー

Outline of Final Research Achievements

Our group has established a rat-derived mast cell line RS-ATL8 cells expressing human FceRI and developed the EXiLE for detecting antigen-specific IgE antibodies present in human serum. This system retains normally IgE signaling-induced degranulation responses and can be used in research for signal molecules in mast cell. In this study, we searched for molecules that regulate mast cell degranulation. With the library of food-derived compounds and 220 protein kinase agonists / antagonists classified by kinome, we found 21 compounds that regulate mast cell degranulation. Ontology analysis suggested the presence of the novel IgE signaling.

Academic Significance and Societal Importance of the Research Achievements

食物アレルギーや花粉症をはじめとする、抗原によるマスト細胞の活性化により惹起されるアレルギー疾患は、科学的知見に基づく医療を受けることで症状のコントロールがおおむね可能となってきているが、全ての患者がその恩恵を受けているわけではないという現状が指摘されており、診療・管理ガイドラインにのっとった医療のさらなる普及が望まれている。

Research Products

• [Journal Article] Cross-allergenicity of crustacean and the edible insect Gryllus bimaculatus in patients with shrimp allergy. (2019)
  • Author(s): Kamemura N, Sugimoto M, Tamehiro N, Adachi R, Tomonari S, Watanabe T, Mito T.
  • Journal Title: Mol Immunol. Volume: 106 Pages: 127-127
  • Peer Reviewed
• [Journal Article] Real-time PCR Detection Methods for Food Allergens (Wheat, Buckwheat, and Peanuts) Using Reference Plasmids. (2019)
  • Author(s): Miyazaki A, Watanabe S, Ogata K, Nagatomi Y, Kokutani R, Minegishi Y, Tamehiro N, Sakai S, Adachi R, Hirao T.
  • Journal Title: J Agric Food Chem. Volume: 67 Pages: 5680-5680
  • Peer Reviewed
• [Journal Article] Ras homolog gene family H (RhoH) deficiency induces psoriasis-like chronic dermatitis by promoting TH17 cell polarization. (2019)
  • Author(s): Tamehiro N, Nishida K, Sugita Y, Hayakawa K, Oda H, Nitta T, Nakano M, Nishioka A, Yanobu-Takanashi R, Goto M, Okamura T, Adachi R, Kondo K, Morita A, Suzuki H.
  • Journal Title: J Allergy Clin Immunol Volume: 143 Pages: 1878-1878
  • Peer Reviewed
• [Journal Article] Determining Food Allergens by Skin Sensitization in Mice. (2018)
  • Author(s): Tamehiro N, Adachi R, Kimura Y, Sakai S, Teshima R, Kondo K
  • Journal Title: Curr Protoc Toxicol. Volume: 76 Issue: 1
  • DOI: 10.1002/cptx.48
  • Peer Reviewed
• [Journal Article] T-cell activation RhoGTPase-activating protein plays an important role in TH17-cell differentiation. (2017)
  • Author(s): Tamehiro N, Nishida K, Yanobu-Takanashi R, Goto M, Okamura T, Suzuki H.
  • Journal Title: Immunol Cell Biol. Volume: 95 Issue: 8 Pages: 729-735
  • DOI: 10.1038/icb.2017.27
  • Peer Reviewed
• [Presentation] Functional food ingredients modulate mast cell signaling (2020)
  • Author(s): Tamehiro N., Adachi R., Kondo K.
  • Organizer: JSA/WAO Joint Congress 2020
  • Int'l Joint Research
• [Presentation] マスト細胞機能制御における分子機構の解析 (2019)
  • Author(s): 為広紀正、安達玲子、廣實慶彦、近藤一成
  • Organizer: アレルギー学会
• [Presentation] コチニールアレルギーモデルを用いたアレルギー病態の解析 (2018)
  • Author(s): 為広紀正、安達玲子、近藤一成
  • Organizer: アレルギー学会
• [Presentation] EXiLE法によるコチニールアレルギー患者IgEの抗原性解析 (2017)
  • Author(s): 為広紀正、安達玲子、中村政志、竹尾直子、山口正雄、安達玲子、中村政志、竹尾直子、山口正雄、中村亮介、永井晶代、矢上晶子、松永佳世子、近藤一成
  • Organizer: 日本アレルギー学会
• [Book] Models of Allergic Disease（Series: Methods in Molecular Biology） (2020)
  • Author(s): Tamehiro N., Adachi R., Kondo K.
  • Total Pages: 11
  • Publisher: Springer Nature