Regulation of myelopoiesis by the transcription factor IRF8

Tomohiko Tamura, Daisuke Kurotaki, Shin ichi Koizumi

研究成果: Contribution to journalReview article査読

65 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)342-351
ページ数10
ジャーナルInternational journal of hematology
101
4
DOI
出版ステータス出版済み - 4 1 2015
外部発表はい

All Science Journal Classification (ASJC) codes

  • 血液学

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