Molecular mechanisms underlying early dendritic cell lineage specification

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03691
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kumamoto University (2021); Yokohama City University (2019-2020)
• Principal Investigator: Kurotaki Daisuke 熊本大学, 国際先端医学研究機構, 特任准教授 (10568455)
• Co-Investigator(Kenkyū-buntansha): 中林 潤 横浜市立大学, 先端医科学研究センター, 准教授 (80322733)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 樹状細胞 / 分化 / 感染 / 遺伝子発現制御

Outline of Final Research Achievements

Various types of hematopoietic cells are derived from bone marrow hematopoietic stem cells; however, the mechanism of lineage determination to each hematopoietic cell lineage is still unclear. In this study, we have identified a subpopulation of multipotent progenitors that express the transcription factor IRF8. This progenitor subpopulation exhibits dendritic cell lineage biased differentiation potential. Furthermore, we analyzed the role of the early fate determination to the dendritic cell lineage in host defense against pathogens. We found that infection induces IRF8 expression in hematopoietic stem and progenitor cells. A detailed analysis of the Irf8 gene locus revealed the cis-regulatory region and transcription factor involved in the induction of IRF8 expression during infection. Our results indicate that early DC fate specification through IRF8 induction might occur during infection.

Free Research Field

血液学、免疫学

Academic Significance and Societal Importance of the Research Achievements

私たちはどのようにして数十種類もの白血球が産生されるのかについて研究を行っています。最近の私たちの研究によって、造血幹細胞（血液のもとになる細胞）に近い前駆細胞の中に、樹状細胞と呼ばれる免疫細胞のみを産生する亜集団が含まれることがわかりました。私たちは、このような樹状細胞への運命決定の仕組みが感染時に活性化することで樹状細胞の素早い産生が可能になり、効果的な病原体除去に貢献していると考えています。