Analysis of molecular mechanisms required for differentiation potential of naive T cells

• Project/Area Number: 19K22547
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Okinawa Institute of Science and Technology Graduate University
• Principal Investigator: Ishikawa Hiroki 沖縄科学技術大学院大学, 免疫シグナルユニット, 准教授 (30648621)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: T細胞 / 分化 / 転写制御 / RNA / ヘルパーT細胞 / ナイーブT細胞 / 分化制御

Outline of Research at the Start

ヘルパーT細胞は様々な免疫反応において司令塔の役割を担う。ナイーブCD4 T細胞は抗原刺激時の環境に応じて異なるヘルパーT細胞に分化するが、このナイーブCD4 T細胞の分化能がどのように制御しているのかはよく分かっていない。この疑問に答えるために、本研究ではナイーブCD4 T細胞に高く発現するJunB RNAに着目し、その機能を明らかにすることを目指す。

Outline of Final Research Achievements

Naive CD4 T cells differentiate into diverse types of T helper cells or regulatory T cells and play a major role in immune responses. However, the mechanism that regulates multipotency of naive CD4 T cell remains largely unknown. In this study, using mice deficient for Junb RNA isoform (n-Junb) that is specifically expressed in naive CD4 T cells, we found that the loss of n-Junb results in increase of IL-17A expression in Th17 cells, which suggests that n-Junb may regulate ability of naive CD4 T cells to differentiate into Th17 cells.

Academic Significance and Societal Importance of the Research Achievements

CD4+ T細胞は各種自己免疫疾患において重要な役割を担うがその分化・機能を制御する分メカニズムについては不明な点が多く残っている。本研究で明らかにしたn-Junb RNAによるTh17細胞の炎症性サイトカインの発現抑制は、自己免疫疾患を制御する新たなメカニズムであり、今後より詳細な解析を続けることで将来的に自己免疫疾患の新たな治療法の開発に貢献する可能性がある。

Research Products

• [Journal Article] The CCR4-NOT deadenylase complex safeguards thymic positive selection by down-regulating aberrant pro-apoptotic gene expression (2020)
  • Author(s): Ito-Kureha Taku、Miyao Takahisa、Nishijima Saori、Suzuki Toru、Koizumi Shin-ichi、Villar-Briones Alejandro、Takahashi Akinori、Akiyama Nobuko、Morita Masahiro、Naguro Isao、Ishikawa Hiroki、Ichijo Hidenori、Akiyama Taishin、Yamamoto Tadashi
  • Journal Title: Nature Communications Volume: 11 Pages: 6169-6169
  • DOI: 10.1038/s41467-020-19975-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transcriptional Regulation of Differentiation and Functions of Effector T Regulatory Cells (2019)
  • Author(s): Koizumi S and Ishikawa H
  • Journal Title: Cells Volume: 8 Pages: 1-17
  • DOI: 10.3390/cells8080939
  • Peer Reviewed / Open Access