Analysis of importance of thymic vitamin A to helper T cell differentiation using a newly established animal model

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K06796
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Nihon Pharmaceutical University (2017); Hirosaki University (2015-2016)
• Principal Investigator: Yamada Toshiyuki 日本薬科大学, 薬学部, 教授 (20183981)
• Co-Investigator(Kenkyū-buntansha): 土田 成紀 弘前大学, 医学研究科, 客員研究員 (20142862) ; 七島 直樹 弘前大学, 保健学研究科, 講師 (80333730) ; 清水 武史 弘前大学, 医学研究科, 助教 (90374818)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: CD4+T細胞 / 分化 / 胸腺 / レチノイン酸

Outline of Final Research Achievements

In this study, it was revealed that retinoic acid (RA)-reactivity in thymic CD4+CD8+ (DP) T cells is important for proper differentiation of CD4+ T cells. We suggested the possible pathway that RA upregulates expression of its target gene Cryab which is involved in NF-kB activation and nuclear translocation, and activated NF-kB then induce expression of the Gata3 gene, a master regulator of CD4+ T cell-differentiation. It was also shown that thymic dendritic cells are implicated in acquisition of the RA-reactivity of CD4+ T cells in the thymus.
We also demonstrated that high level of expression of the Gata3 gene observed in thymic DP T cells is downregulated in subsequent differentiation stages of CD4+ T cells and alternation of histone modification status in the upstream promoter region of the gene is responsible for the downregulation.

Free Research Field

分子生物学