Clarification of regulatory T cell-specific epigenome

2018 Fiscal Year Final Research Report

• Project/Area Number: 15H04744
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Kyoto University (2018); Osaka University (2015-2017)
• Principal Investigator: Ohkura Naganari 京都大学, ウイルス・再生医科学研究所, 特定研究員 (20300949)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 制御性T細胞 / エピゲノム / DNA脱メチル化

Outline of Final Research Achievements

To reveal the mechanisms for Treg differentiation, we determined Treg-specific DNA hypomethylated regions using whole genome bisulfite sequencing, and examined the association between the regions and Treg-specific characteristics. Treg-hypomethylated regions were highly associated with Treg-specific gene expression, H3K27ac modification, and open chromatin status. In addition, autoimmune disease-associated SNPs were highly accumulated within the regions, but not in the T cell activation-specific hypomethylated regions. These results suggest that autoimmune disease susceptibility would be largely affected by the changes in Treg function rather than those in T cell activation. By single cell analysis of thymic T cells, we also found the path and factors for Treg development, which are different from those of conventional T cells. This information would be useful for the development of therapies or drugs for autoimmune diseases.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により、自己免疫疾患感受性は、活性化T細胞の機能亢進よりむしろTreg機能の低下が要因となっていることが示された。本研究結果は、エピジェネテック変化に関与する遺伝子やクロマチン構造変化をもたらす遺伝子の変異、多型が、自己免疫疾患ひいては慢性炎症の感受性に影響する可能性を示しており、新たな治療法開発の基礎となる成果である。
加えて、胸腺細胞群のsingle cell解析では、Treg分化の最初期に関わる因子を同定した。本因子群は、Tregの人工的誘導等や分化抑制に応用可能であり、自己免疫疾患や悪性腫瘍の新たな治療法への展開が期待できる。