Analysis of the relationship between postnatal FOXP3 epigenetic changes and immune tolerance

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K19667
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Juntendo University
• Principal Investigator: Yamazaki Susumu 順天堂大学, 医学部, 非常勤助教 (80771774)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 免疫 / アレルギー / 新生児 / 小児 / 自己免疫 / 制御性T細胞 / エピジェネティクス / ヒストン脱アセチル化酵素

Outline of Final Research Achievements

Background: Characterization of regulatory T cells (Tregs) is important for the treatment and prevention of autoimmune diseases and allergies. Tregs are known to be actively induced throughout the fetal and neonatal periods. However, it is unknown why Tregs are induced more in the perinatal period than in adults. This study investigated the hypothesis that neonatal ability to inhibit HDAC activity is related to Tregs induction at the fetal and neonatal stage. Methods: The ability of umbilical cord blood and adult serum to inhibit HDAC was compared by enzyme assays. Results: Neonatal blood had significantly higher ability to inhibit HDAC11 activity than did the blood from adults (P<0.005). Conclusion: This is the first comparison of the ability to inhibit HDAC activity between adult and neonatal human sera.Since HDAC11 is known to inhibit the expression of FOXP3, our results suggest that Tregs are induced by the increased inhibition of HDAC11 during the perinatal period.

Free Research Field

免疫

Academic Significance and Societal Importance of the Research Achievements

本研究では、新生児期において制御性T細胞が優位な理由の一端としてHDAC11が関わる可能性を示した。制御性T細胞は免疫寛容（過剰な炎症を抑える働き）に重要な役割を担う細胞で、アレルギー疾患や自己免疫疾患のみならず、悪性腫瘍、不妊・早産でもその重要性が指摘されている。特に、食物アレルギーでは食物抗原に対して、不妊・早産では母体の精子・胎児に対して免疫寛容が不十分な状態が原因の一端ともされている。本研究で指摘したHDAC11はこれら疾患の新たな治療ターゲットとなり得る可能性がある。