The transcription factor Fli-1 regulates monocyte, macrophage and dendritic cell development in mice

被引:32
作者
Suzuki, Eiji [1 ]
Williams, Sarah [2 ]
Sato, Shuzo [1 ]
Gilkeson, Gary [1 ,2 ]
Watson, Dennis K. [3 ]
Zhang, Xian K. [1 ,2 ]
机构
[1] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA
[2] Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC USA
[3] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA
基金
美国国家卫生研究院;
关键词
dendritic cells; Fli-1 transcription factor; Fms-related tyrosine kinase 3 ligand; macrophages; monocytes; MARGINAL ZONE; ETS FAMILY; IN-VIVO; GENE; EXPRESSION; PROLIFERATION; ACTIVATION; MECHANISMS; DOMAIN; MEMBER;
D O I
10.1111/imm.12070
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Fli-1 belongs to the Ets transcription factor family and is expressed in haematopoietic cells, including most of the cells that are active in immunity. The mononuclear phagocytes, i.e. monocytes, macrophages and dendritic cells, originate in haematopoietic stem cells and play an important role in immunity. To assess the role of Fli-1 in mononuclear phagocyte development in vivo, we generated mice that express a truncated Fli-1 protein, lacking the C-terminal transcriptional activation domain (Fli-1CTA). Fli-1CTA/CTA mice had significantly increased populations of haematopoietic stem cells and common dendritic cell precursors in bone marrow compared with wild-type littermates. Significantly increased classical dendritic cells, plasmacytoid dendritic cells, and macrophage populations were found in spleens from Fli-1CTA/CTA mice compared with wild-type littermates. Fli-1CTA/CTA mice also had increased pre-classical dendritic cell and monocyte populations in peripheral blood mononuclear cells. Furthermore, bone marrow reconstitution studies demonstrated that expression of Fli-1 in both haematopoietic cells and stromal cells affected mononuclear phagocyte development in mice. Expression of Fms-like tyrosine kinase 3 ligand (Flt3L), a haematopoietic growth factor, in multipotent progenitors was statistically significantly increased from Fli-1CTA/CTA mice compared with wild-type littermates. Fli-1 protein binds directly to the promoter region of the Flt3L gene. Hence, Fli-1 plays an important role in the mononuclear phagocyte development, and the C-terminal transcriptional activation domain of Fli-1 negatively modulates mononuclear phagocyte development.
引用
收藏
页码:318 / 327
页数:10
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