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

Haruka Sasaki, Daisuke Kurotaki, Naoki Osato, Hideaki Sato, Izumi Sasaki, Shin-ichi Koizumi, Hongsheng Wang, Chika Kaneda, Akira Nishiyama, Tsuneyasu Kaisho, Hiroyuki Aburatani, Herbert C. Morse III, Keiko Ozato and Tomohiko Tamura

Key points

  • IRF8 promotes Gata2 expression in granulocyte progenitors, thereby playing a key role in the development of basophils and mast cells.

Abstract

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 absence of pre-basophil and mast cell progenitors (pre-BMPs). Although Irf8-/- mice retained peripheral tissue mast cells, remaining progenitors from Irf8-/- mice including granulocyte progenitors (GPs) were unable to efficiently generate either basophils or mast cells, indicating that IRF8 also contributes to the development of mast cells. IRF8 appeared to function at the GP stage, since IRF8 was expressed in GPs but not in basophils, mast cells, and basophil/mast cell-restricted progenitor cells. Furthermore, we demonstrate that GATA2, a transcription factor known to promote basophil and mast cell differentiation, acts downstream of IRF8. These results shed light on the pathways and the mechanism underlying the development of basophils and mast cells.

  • Submitted February 24, 2014.
  • Accepted November 6, 2014.