Transcription factor IRF8 plays a critical role in the development of murine basophils and mast cells.

  title={Transcription factor IRF8 plays a critical role in the development of murine basophils and mast cells.},
  author={Haruka Sasaki and Daisuke Kurotaki and Naoki Osato and Hideaki Sato and Izumi Sasaki and Shinji Koizumi and Hongsheng Wang and Chika Kaneda and Akira Nishiyama and Tsuneyasu Kaisho and Hiroyuki Aburatani and Herbert C. Morse and Keiko Ozato and Tomohiko Tamura},
  volume={125 2},
Basophils and mast cells play critical roles in host defense against pathogens and allergic disorders. However, the molecular mechanism by which these cells are generated is not completely understood. Here we demonstrate that interferon regulatory factor-8 (IRF8), a transcription factor essential for the development of several myeloid lineages, also regulates basophil and mast cell development. Irf8(-/-) mice displayed a severe reduction in basophil counts, which was accounted for by the… 

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Regulation of basophil and mast cell development by transcription factors.

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Transcriptional and Epigenetic Regulation of Innate Immune Cell Development by the Transcription Factor, Interferon Regulatory Factor-8.

  • D. KurotakiT. Tamura
  • Biology
    Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
  • 2016
Recent advances in the understanding of transcriptional and epigenetic regulation involving IRF8 in the development of myeloid cells are discussed.

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Basophils and mast cells, which are selectively endowed with the high-affinity IgE receptor and mediate a range of adaptive and innate immune responses, have an unknown developmental relationship.

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It is found that naive mice lacking the transcription factor, interferon regulatory factor 2 (IRF-2), exhibited signal transducer and activator of transcription 6 (Stat6)-independent expansion of basophils in the periphery, and that basophil acted as a cellular converter to turn the neutral IL-3 into the Th2-inducing IL-4 during the initiation of Th1/Th2 differentiation.

GATA-1 regulates the generation and function of basophils

It is demonstrated that GATA-1 plays a key role in the generation and function of basophils and underscore the need for careful distinction of the cell lineage responsible for each phenotype observed in ΔdblGATA mice.

Critical role of P1-Runx1 in mouse basophil development.

The results of the present study suggest that P1-Runx1 is critical for a stage of basophil development between SN-Flk2(+/-) cells and basophils progenitors.

Shared and Distinct Functions of the Transcription Factors IRF4 and IRF8 in Myeloid Cell Development

It is shown that IRF4 has activities similar to IRF8 in regulating myeloid cell development, and it is demonstrated that Irf8 -/- Irf4 -/- mice exhibit a more severe chronic myeloids leukemia (CML)-like disease than IrF8 -/+ mice, involving a disproportionate expansion of granulocytes at the expense of monocytes/macrophages.

Essential role for ICSBP in the in vivo development of murine CD8alpha + dendritic cells.

It is demonstrated that ICSBP is critically required for the in vivo differentiation of CD8 alpha(+) DCs and may also influence the functional maturation of the CD8alpha(-) subsets.

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

Irf8(-/-) haematopoietic progenitors not only bestows monocyte and DC differentiation potential upon mononuclear phagocytes but also restrains these progenitor from differentiating into neutrophils.

Inflammatory Flt3l is essential to mobilize dendritic cells and for T cell responses during Plasmodium infection

An innate sensing pathway triggered by Plasmodium infection that regulates dendritic cell homeostasis and adaptive immunity through Flt3 ligand (Flt3l) release is described and found that type I IFN supports the upregulation of xanthine dehydrogenase.