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

被引:118
作者
Kurotaki, Daisuke [1 ]
Yamamoto, Michio [1 ]
Nishiyama, Akira [1 ]
Uno, Kazuhiro [1 ]
Ban, Tatsuma [1 ]
Ichino, Motohide [1 ]
Sasaki, Haruka [1 ]
Matsunaga, Satoko [2 ]
Yoshinari, Masahiro [1 ]
Ryo, Akihide [2 ]
Nakazawa, Masatoshi [3 ]
Ozato, Keiko [4 ]
Tamura, Tomohiko [1 ]
机构
[1] Yokohama City Univ, Grad Sch Med, Dept Immunol, Yokohama, Kanagawa 2360004, Japan
[2] Yokohama City Univ, Grad Sch Med, Dept Microbiol, Yokohama, Kanagawa 2360004, Japan
[3] Yokohama City Univ, Grad Sch Med, Dept Expt Anim Sci, Yokohama, Kanagawa 2360004, Japan
[4] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA
来源
NATURE COMMUNICATIONS | 2014年 / 5卷
基金
日本学术振兴会;
关键词
CD8-ALPHA(+) DENDRITIC CELLS; SEQUENCE-BINDING-PROTEIN; C/EBP-ALPHA; TRANSCRIPTION FACTOR; REGULATORY FACTOR-8; LINEAGE COMMITMENT; HEMATOPOIETIC STEM; GRANULOCYTIC DIFFERENTIATION; IN-VIVO; MACROPHAGES;
D O I
10.1038/ncomms5978
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Myeloid progenitors lose their potential to generate neutrophils when they adopt the mononuclear phagocyte lineage. The mechanism underlying this lineage restriction remains unknown. We here report that the protein expression of IRF8, an essential transcription factor for the development of dendritic cells (DCs) and monocytes, sharply increases at the monocyte-DC progenitor (MDP) stage and remains high in common monocyte progenitors (cMoPs). Irf8(-/-) MDPs and cMoPs accumulate but fail to efficiently generate their downstream populations, instead giving rise to neutrophils in vivo. IRF8 physically interacts with the transcription factor C/EBP alpha and prevents its binding to chromatin in MDPs and cMoPs, blocking the ability of C/EBP alpha to stimulate transcription and neutrophil differentiation. A partial inhibition of C/EBP activity in Irf8(-/-) haematopoietic progenitors alleviates the neutrophil overproduction in vivo. Thus, IRF8 not only bestows monocyte and DC differentiation potential upon mononuclear phagocyte progenitors but also restrains these progenitors from differentiating into neutrophils.
引用
收藏
页数:15
相关论文
共 51 条
  • [1] Essential role for ICSBP in the in vivo development of murine CD8α+ dendritic cells
    Aliberti, J
    Schulz, O
    Pennington, DJ
    Tsujimura, H
    Sousa, CRE
    Ozato, K
    Sher, A
    [J]. BLOOD, 2003, 101 (01) : 305 - 310
  • [2] IRF-8 extinguishes neutrophil production and promotes dendritic cell lineage commitment in both myeloid and lymphoid mouse progenitors
    Becker, Amy M.
    Michael, Drew G.
    Satpathy, Ansuman T.
    Sciammas, Roger
    Singh, Harinder
    Bhattacharya, Deepta
    [J]. BLOOD, 2012, 119 (09) : 2003 - 2012
  • [3] C/EBPα regulates osteoclast lineage commitment
    Chen, Wei
    Zhu, Guochun
    Hao, Liang
    Wu, Mengrui
    Ci, Hongliang
    Li, Yi-Ping
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (18) : 7294 - 7299
  • [4] Forming functional fat: a growing understanding of adipocyte differentiation
    Cristancho, Ana G.
    Lazar, Mitchell A.
    [J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2011, 12 (11) : 722 - 734
  • [5] Interferon regulatory factors are transcriptional regulators of adipogenesis
    Eguchi, Jun
    Yan, Qing-Wu
    Schones, Dustin E.
    Karnal, Michael
    Hsu, Chung-Hsin
    Zhang, Michael Q.
    Crawford, Gregory E.
    Rosen, Evan D.
    [J]. CELL METABOLISM, 2008, 7 (01) : 86 - 94
  • [6] A clonogenic bone marrow progenitor specific for macrophages and dendritic cells
    Fogg, DK
    Sibon, C
    Miled, C
    Jung, S
    Aucouturier, P
    Littman, DR
    Cumano, A
    Geissmann, F
    [J]. SCIENCE, 2006, 311 (5757) : 83 - 87
  • [7] Transcriptional control of granulocyte and monocyte development
    Friedman, A. D.
    [J]. ONCOGENE, 2007, 26 (47) : 6816 - 6828
  • [8] IDENTIFICATION OF 2 POLYPEPTIDE SEGMENTS OF CCAAT ENHANCER-BINDING PROTEIN REQUIRED FOR TRANSCRIPTIONAL ACTIVATION OF THE SERUM-ALBUMIN GENE
    FRIEDMAN, AD
    MCKNIGHT, SL
    [J]. GENES & DEVELOPMENT, 1990, 4 (08) : 1416 - 1426
  • [9] Development of Monocytes, Macrophages, and Dendritic Cells
    Geissmann, Frederic
    Manz, Markus G.
    Jung, Steffen
    Sieweke, Michael H.
    Merad, Miriam
    Ley, Klaus
    [J]. SCIENCE, 2010, 327 (5966) : 656 - 661
  • [10] IRF8 Mutations and Human Dendritic-Cell Immunodeficiency
    Hambleton, Sophie
    Salem, Sandra
    Bustamante, Jacinta
    Bigley, Venetia
    Boisson-Dupuis, Stephanie
    Azevedo, Joana
    Fortin, Anny
    Haniffa, Muzlifah
    Ceron-Gutierrez, Lourdes
    Bacon, Chris M.
    Menon, Geetha
    Trouillet, Celine
    McDonald, David
    Carey, Peter
    Ginhoux, Florent
    Alsina, Laia
    Zumwalt, Timothy J.
    Kong, Xiao-Fei
    Kumararatne, Dinakantha
    Butler, Karina
    Hubeau, Marjorie
    Feinberg, Jacqueline
    Al-Muhsen, Saleh
    Cant, Andrew
    Abel, Laurent
    Chaussabel, Damien
    Doffinger, Rainer
    Talesnik, Eduardo
    Grumach, Anete
    Duarte, Alberto
    Abarca, Katia
    Moraes-Vasconcelos, Dewton
    Burk, David
    Berghuis, Albert
    Geissmann, Frederic
    Collin, Matthew
    Casanova, Jean-Laurent
    Gros, Philippe
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2011, 365 (02) : 127 - 138