The Transcription Factor PU.1 Controls Dendritic Cell Development and Flt3 Cytokine Receptor Expression in a Dose-Dependent Manner

被引：225

作者：

Carotta, Sebastian ^{[1
]}

Dakic, Aleksandar ^{[1
]}

D'Amico, Angela ^{[1
]}

Pang, Swee Heng Milon ^{[1
,2
]}

Greig, Kylie T. ^{[1
,2
]}

Nutt, Stephen L. ^{[1
]}

Wu, Li ^{[1
]}

机构：

[1] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia

[2] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia

来源：

IMMUNITY | 2010年 / 32卷 / 05期

基金：

英国医学研究理事会; 澳大利亚研究理事会;

关键词：

LINEAGE-COMMITMENT; TARGETED DISRUPTION; C/EBP-ALPHA; STEM-CELLS; LIGAND; PROGENITORS; MACROPHAGE; IDENTIFICATION; MAINTENANCE; GENERATION;

D O I：

10.1016/j.immuni.2010.05.005

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The transcription factor PU.1 plays multiple context and concentration dependent roles in lymphoid and myeloid cell development. Here we showed that PU.1 (encoded by Sfpi1) was essential for dendritic cell (DC) development in vivo and that conditional ablation of PU.1 in defined precursors, including the common DC progenitor, blocked Flt3 ligand-induced DC generation in vitro. PU.1 was also required for the parallel granulocyte-macrophage colony stimulating factor-induced DC pathway from early hematopoietic progenitors. Molecular studies demonstrated that PU.1 directly regulated Flt3 in a concentration-dependent manner, as Sfpi1(+/-) cells displayed reduced expression of Flt3 and impaired DC formation. These studies identify PU.1 as a critical regulator of both conventional and plasmacytoid DC development and provide one mechanism how altered PU.1 concentration can have profound functional consequences for hematopoietic cell development.

引用

页码：628 / 641

页数：14

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