Transcription factor IRF8 plays a critical role in the development of murine basophils and mast cells.
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, because 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 mechanism underlying the development of basophils and mast cells.
Department of Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan;
Haruka
H
Sasaki
Department of Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan;
Daisuke
D
Kurotaki
Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan;
Naoki
N
Osato
Department of Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan;
Hideaki
H
Sato
Laboratory for Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan;
Izumi
I
Sasaki
Department of Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan;
Shin-ichi
S
Koizumi
Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD;
Hongsheng
H
Wang
Department of Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan;
Chika
C
Kaneda
Department of Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan;
Akira
A
Nishiyama
Laboratory for Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan; Laboratory for Inflammatory Regulation, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan; and.
Tsuneyasu
T
Kaisho
Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan;
Hiroyuki
H
Aburatani
Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD;
Herbert C
HC
Morse
Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
Keiko
K
Ozato
Department of Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan;
Tomohiko
T
Tamura
D000818:Animals; D001491:Basophils / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D050989:GATA2 Transcription Factor / Q000276:immunology* / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000276:immunology* / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism; D000099185:Interferon Regulatory Factor-8
D050989:GATA2 Transcription Factor; D050835:Interferon Regulatory Factors; D014157:Transcription Factors; D000099185:Interferon Regulatory Factor-8; C494712:Gata2 protein, mouse