Regulation of myelopoiesis by the transcription factor IRF8

Tomohiko Tamura, Daisuke Kurotaki, Shin ichi Koizumi

Research output: Contribution to journalReview articlepeer-review

61 Citations (Scopus)

Abstract

Interferon regulatory factor-8 (IRF8) is a transcription factor expressed in hematopoietic cells, particularly in mononuclear phagocytes [monocytes/macrophages and dendritic cells (DCs)] and their progenitors. Various studies have demonstrated that IRF8 is essential for the development of monocytes, DCs, eosinophils, and basophils. Conversely, IRF8 suppresses the generation of neutrophils. Accordingly, Irf8−/− mice develop immunodeficiency and a chronic myeloid leukemia (CML)-like disease. Mutations and loss of expression of the human IRF8 gene are also associated with immunodeficiency and CML, respectively. Recent findings have begun to reveal the transcription factor network and epigenetic changes governed by IRF8. For example, in mononuclear phagocyte progenitors, IRF8 cooperates with PU.1 to promote the formation of promoter-distal enhancers to induce monocyte-related genes including the critical downstream transcription factor gene Klf4. On the other hand, IRF8 blocks C/EBPα activity to suppress the neutrophil differentiation program. Indeed, Irf8−/− mononuclear phagocyte progenitors fail to efficiently generate monocytes and DCs and, instead, aberrantly give rise to neutrophils. This article provides an overview of recent advances in our understanding of the role of IRF8 in myelopoiesis and related diseases.

Original languageEnglish
Pages (from-to)342-351
Number of pages10
JournalInternational journal of hematology
Volume101
Issue number4
DOIs
Publication statusPublished - Apr 1 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hematology

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