Cellular and molecular mechanism of neonatal immune tolerance in term and preterm infants

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08293
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: The University of Tokyo
• Principal Investigator: Takahashi Naoto 東京大学, 医学部附属病院, 教授 (50197159)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 新生児免疫寛容 / 制御性T細胞 / スーパー抗原 / 臍帯血 / FoxP3 / Helios

Outline of Final Research Achievements

The aim of the study is to elucidate cellular and molecular mechanism of neonatal immune tolerance in human. Cord blood (CB) T cells showed a significantly higher level of FoxP3 expression induced by a primary stimulation with a superantigen than adult peripheral blood (APB). CB mononuclear cells showed a lower expression level of IL2 gene and a higher expression of genes related to regulatory T cells (Treg) namely FoxP3 induced by secondary stimulation with a superantigen. IKFZ2 gene (Helios) was consistently expressed at a higher level in CB T cells than APB T cells. A possible mechanism of neonatal immune tolerance can be active induction of immune suppression with Treg and is related to expression of genes of Helios and FoxP3. We think that the findings seen in neonates is consistent with that reported in immune system of fetus in utero in the past papers.

Free Research Field

新生児免疫

Academic Significance and Societal Importance of the Research Achievements

新生児免疫寛容は新生児の易感染性の原因や臍帯血移植の際の拒絶反応の弱さと関係していると考えられて来たが、その細胞分子学的機序は十分には解明されて来ていない。一方、制御性T細胞の発見と胎児期にその細胞分画が多いことから、我々は新生児免疫寛容はむしろ能動的に行われている可能性が高いと考えた。今回の研究結果は、その考えを証明しており、また関係する転写因子としてFoxP3やHeliosを候補として同定することができた。今後はさらにこれら転写因子の発現調節機構を明らかにすることにより、新生児の易感染性の改善や臍帯血移植をより効果的に行う方法の開発などの研究に役立てることが可能と考えれられる。