YOKOHAMA CITY UNIVERSITY

IRF8 inhibits ​C/EBPα activity to restrain mononuclear phagocyte progenitors from differentiating into neutrophils

Home > Research > IRF8 inhibits ​C/EBPα activity to restrain mononuclear phagocyte progenitors from differentiating into neutrophils
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Myeloid progenitors lose their potential to generate neutrophils when they adopt the mononuclear phagocyte lineage. The mechanism underlying this lineage restriction remains unknown. We here report that the protein expression of ​IRF8, an essential transcription factor for the development of dendritic cells (DCs) and monocytes, sharply increases at the monocyte-DC progenitor (MDP) stage and remains high in common monocyte progenitors (cMoPs). ​Irf8 MDPs and cMoPs accumulate but fail to efficiently generate their downstream populations, instead giving rise to neutrophils in vivo. ​IRF8 physically interacts with the transcription factor ​C/EBPα and prevents its binding to chromatin in MDPs and cMoPs, blocking the ability of ​C/EBPα to stimulate transcription and neutrophil differentiation. A partial inhibition of C/EBP activity in ​Irf8 haematopoietic progenitors alleviates the neutrophil overproduction in vivo. Thus, ​IRF8 not only bestows monocyte and DC differentiation potential upon mononuclear phagocyte progenitors but also restrains these progenitors from differentiating into neutrophils.

Tomohiko Tamura
Professor, Yokohama City University, Department of Immunology, Graduate School of Medicine
Phone: +81-45-787-2614
e-mail: tamurat@yokohama-cu.ac.jp
URL: http://www-user.yokohama-cu.ac.jp/~immunol/

 

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