Regulation of myelopoiesis by the transcription factor IRF8

International Journal of Hematology
Tomohiko TamuraShin-ichi Koizumi

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 ...Continue Reading

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Citations

Mar 11, 2015·International Journal of Hematology·Tomohiko Tamura
Mar 15, 2016·Allergology International : Official Journal of the Japanese Society of Allergology·Haruka SasakiTomohiko Tamura
Nov 13, 2015·Seminars in Immunology·Chiara PortaAntonio Sica
Jul 15, 2015·Biochemical and Biophysical Research Communications·Akihiro TamuraTaira Maekawa
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Jul 6, 2016·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Daisuke Kurotaki, Tomohiko Tamura
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Apr 6, 2017·International Immunology·Daisuke KurotakiTomohiko Tamura
May 20, 2017·International Journal of Hematology·Akihiro TamuraYoshiyuki Kosaka
Mar 30, 2017·Nature·Aurélie HéraultEmmanuelle Passegué
Oct 4, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Qian LiYubin Zhang
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