Development of the novel screening method for reprogramming of inflammatory environment

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02673
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: Sekiya Takashi 国立研究開発法人国立国際医療研究センター, その他部局等, 免疫応答修飾研究室長 (80519207)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 免疫 / 細胞リプログラミング / 制御性T細胞

Outline of Final Research Achievements

The objective of this research is to develop a novel recombinant protein library (called "IFDR library" herein), in which effective molecules are highly enriched than previous ones, and identify molecules which have an ability to modulate the function of regulatory T (Treg) cells in pathogenic environments, by utilizing the this novel library.
First, this research has succeeded in scaling up the screening of the IFDR library, by finding an optimal signal peptide, cell line, and drug resistance gene. Then, applying this improved IFDR library for the screening, I identified two molecules (termed 9-7F-6 and 18-11F-7) that have an ability to repress the function of Treg cells. I then purified the recombinant proteins of the two molecules from the culture supernatant of 293T cells, and applied the recombinant proteins for further investigation. As a result, it was revealed that 9-7F-6 and 18-11F-7 interacted with Treg and antigen presenting cells, respectively.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

DNA, RNA等の核酸ライブラリは、構築・改良が重ねられてきているが、タンパク質ライブラリの簡便な作製法は存在しないのが現状と言える。しかし、本研究により、多種類の組み換えタンパク質を含むライブラリの簡便な作製法が新たに構築された。
多細胞生物における細胞間相互作用の多くはタンパク分子により担われるため、本ライブラリの応用により、免疫応答を制御する分子のみならず、様々な生物学的意義を持つ分子の同定が可能になると期待される。
さらに、本ライブラリの応用で見出したTregの機能を制御する分子は、炎症性疾患や腫瘍など、Tregの機能異常が関与する疾患における治療標的としての展開が期待できる。