Regulation of novel inflammatory helper T cells differentiation at low concentration of retinoic acid

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07026
• 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: Tokushima Bunri University
• Principal Investigator: Ohoka Yoshiharu 徳島文理大学, 薬学部, 教授 (60303971)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: NRIP / Th9 / レチノイン酸 / リガンド依存的コリプレッサー / TGF-β

Outline of Final Research Achievements

Th9 cells are a newly identified inflammatory helper T cell subset that primarily produce IL-9 and have been reported to be involved in the pathogenesis of allergic airway inflammation such as bronchial asthma and in tumor immunity. It has been suggested that Th9 cell differentiation is negatively regulated by retinoic acid signaling. In this study, we explored the involvement of ligand-dependent repressors in the negative regulatory mechanism of Th9 cell differentiation. As a result, we found that ligand-dependent repressor: NRIP is specifically expressed in Th9 cells and is actually involved in the repression of IL-9 gene expression. Furthermore, we investigated the regulatory mechanism of the NRIP gene expression in Th9 cells. We found that NRIP gene expression requires TGF-β signaling, which are involved in the induction of Th9 cell differentiation and retinoic acid.

Free Research Field

免疫学 生化学　分子生物学

Academic Significance and Societal Importance of the Research Achievements

Th9細胞は主にIL-9を産生する新規に同定されたヘルパーT細胞サブセットで、気管支喘息等のアレルギー性気道炎症の病態に関与していることや腫瘍免疫への関与が報告されている。Th9細胞の分化制御にレチノイン酸による負の制御機構が関与することは知られていたが、その詳細な機構は明らかでは無かった。本研究において、リガンド依存的コリプレッサー：NRIPがTh9細胞のレチノイン酸による負の分化制御機構に関与していることを見出し、NRIP遺伝子の発現制御機構の一端を明らかにした。これらの研究成果はアレルギーや自己免疫疾患の新たな病態の解明や治療薬開発の分子基盤の構築にも貢献することが期待できる。