The role of Gfi1 in the differentiation of mast cells

• Project/Area Number: 18K06650
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: National Institutes of Biomedical Innovation, Health and Nutrition
• Principal Investigator: YAMAGUCHI Tomoko 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 幹細胞制御プロジェクト, 研究員 (50580130)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: マスト細胞 / 分化 / Gfi1

Outline of Final Research Achievements

Mast cells are primary effectors not only in allergic disorders, but also in other immune diseases such as chronic inflammatory disorders. Mast cells are generally classified into two phenotypically distinct populations: mucosal-type mast cells (MMCs) and connective tissue-type mast cells (CTMCs). However, the molecular basis determining the different characteristics of the mast cell subclasses still remains unclear. In this study, we generate knock-out (KO) mice and analyze the number of mast cells in the KO mice. Our results showed that the number of mast cell progenitors and CTMCs was decreased in KO mice. In addition, engraftment of WT bone marrow cells in w-sh/w-sh recipients restored the generation of CTMCs to normal levels. In contrast, engraftment of KO bone marrow cells in w-sh/w-sh mice failed to restore mast cell generation. These results showed that differentiation of CTMCs might be regulated by Gfi1.

Academic Significance and Societal Importance of the Research Achievements

本研究により、マスト細胞分化の分子機構の一端が解明できれば、将来的にはマスト細胞の分化・成熟化を標的としたこれまでとは異なった作用機序を有する新規アレルギー治療法の開発が期待される。

Research Products

• [Journal Article] The role of galanin in the differentiation of mucosal mast cells in mice. (2020)
  • Author(s): Yamaguchi T., Ikeda Y., Tashiro K., Ohkawa Y., Kawabata K.
  • Journal Title: Eur. J. Immunol. Volume: 50 Issue: 1 Pages: 110-118
  • DOI: 10.1002/eji.201848061
  • Peer Reviewed / Open Access
• [Presentation] マスト細胞分化における転写因子Gfi1の役割 (2019)
  • Author(s): 山口朋子、田中智之、西島美妙江、長竹貴広、國澤純、川端健二
  • Organizer: 第68回日本薬学会近畿支部総会・大会