Elucidation of the influence of histone deacetylase inhibitory ability during the neonatal period on the development of allergic diseases

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K17310
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Juntendo University
• Principal Investigator: Yamazaki Susumu 順天堂大学, 医学部, 助教 (80771774)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: アレルギー / エピジェネティクス

Outline of Final Research Achievements

This study measured HDAC inhibitory ability and butyrate levels in the blood of children with food allergies (FA), and confirmed the hypothesis that FA children have low serum butyrate levels and low ability to inhibit HDAC11 activity, resulting in weak immune tolerance and are more prone to allergic reactions. I tried to prove it.
We analyzed serum acetoacetate, β-OHB, total ketone bodies, and serum HDAC inhibitory ability (HDAC1-11) in children with food allergies and healthy adults but found no significant differences as observed in the neonatal period (cord blood). No difference was observed in HDAC inhibitory ability and serum β-OHB between the two groups. On the other hand, it was also confirmed that sample serum with a butyrate concentration lower than the reagent butyrate concentration had higher HDAC inhibitory ability, confirming that factors other than butyrate also play a major role in determining HDAC inhibitory ability.

Free Research Field

アレルギー

Academic Significance and Societal Importance of the Research Achievements

食物アレルギーの発症予防や発症原因の究明は未だ途上である。本研究は先行研究において臍帯血の酪酸値とHDAC11阻害能が成人検体に比べ高値でありそれによる免疫寛容が盛んであるという仮説から着想を得た研究である。本研究は酪酸はHDAC11阻害能を確実に持ち、FOXP3の発現を更新させる可能性は示せたが、一方で食物アレルギー児で酪酸濃度が低い訳ではなく、また血清酪酸濃度のみでHDAC阻害能全てを賄うと説明するには不十分であることが判明した。酪酸の摂取によるFOXP3の発現亢進、さらにはアレルギー発症予防という単純な結果は得られなかったが、アレルギー発症予防の研究の一旦は担ったと考えられる。