Study on the mechanism of mononuclear phagocyte development

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390246
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Yokohama City University
• Principal Investigator: TAMURA Tomohiko 横浜市立大学, 医学(系)研究科(研究院), 教授 (50285144)
• Co-Investigator(Renkei-kenkyūsha): NISHIYAMA Akira 横浜市立大学, 医学(系)研究科(研究院), 准教授 (80589664) ; KUROTAKI Daisuke 横浜市立大学, 医学部, 助教 (10568455) ; OSATO Naoki 東京大学, 先端科学技術研究センター, 特任研究員 (50509536)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 発生・分化 / 遺伝子 / 発現制御 / 転写因子

Outline of Final Research Achievements

Transcription factors play critical roles in cell differentiation. In this study, we aimed at understanding the molecular mechanism of differentiation towards mononuclear phagocytes, such as monocytes and dendritic cells, by investigating the role of the transcription factor IRF8. We found that IRF8 expression sharply increases at the mononuclear phagocyte progenitor stages and interacts with other transcription factors, thereby stimulating the differentiation towards monocytes and dendritic cells, while preventing the differentiation towards non-mononuclear phagocytes, neutrophils. When promoting the differentiation, IRF8 induces the formation of chromatin regions called enhancers to stimulate transcription of many critical target genes. Moreover, we found that IRF8 overrides the oncogene BCR-ABL to rescue dendritic cell development in chronic myeloid leukemia (CML), providing the conceptual basis for developing a new therapy of CML.

Free Research Field

血液学、免疫学、内科学