Analysis of the GATA2-histamine pathway and primary immunodeficiency disease.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15068
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Tohoku Medical and Pharmaceutical University
• Principal Investigator: Takai Jun 東北医科薬科大学, 医学部, 助教 (90813890)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: GATA2 / ヒスタミン / 炎症 / インビボイメージング

Outline of Final Research Achievements

In this study, we focused on the transcription factor GATA2, a critical factor in hematopoietic development, and aimed to elucidate the mechanism by which GATA2 is involved in histamine production and its relationship with GATA2-related diseases. Thus, we performed the following analysis; 1) elucidation of the GATA2-histamine pathway using histamine-producing cell monitoring mice and 2) elucidation of the role of GATA2 in GATA2-related diseases.
In the process of conducting the above research, we succeeded in establishing histamine-producing cell monitoring mice and published experimental results in Scientific reports. In addition, we also found that GATA2 directly binds to the locus of the histamine synthase gene and that GATA2 regulates various cytokines associated with histamine.

Free Research Field

医化学

Academic Significance and Societal Importance of the Research Achievements

GATA2関連疾患であるMonoMAC症候群は2011年に初めて報告された疾患であるが、未だ有効な治療法は確立されてない。本研究の成果を基に、GATA2-ヒスタミン経路が感染免疫応答に関与する詳細な分子機序が解明されれば、monoMAC症候群に有効な治療法開発にも応用することができる。また、GATA2-ヒスタミン経路を特異的に阻害することができれば、新規メカニズムのアレルギー性疾患治療薬の開発にもつながると考えられる。