Journal article
The transcription factor PU.1 controls dendritic cell development and Flt3 cytokine receptor expression in a dose-dependent manner
S Carotta, A Dakic, A D'Amico, SHM Pang, KT Greig, SL Nutt, L Wu
Immunity | Published : 2010
Abstract
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 f..
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Funding Acknowledgements
We thank A. Kallies, K. Shortman, and G. Belz for comments on the manuscript; K. Elder and N. Bernard for technical assistance; and M. Busslinger (IMP, Vienna Austria) for providing the Flt3<SUP>+/-</SUP> mice and plasmid vectors. This work was supported by the National Health and Medical Research Council (NHMRC) of Australia. S.C. was supported by an Australian Research Council Discovery Fellowship, S.H.M.P. by the Leukaemia Foundation, K.T.G. by a Stella Mary Langford Scholarship from the University of Melbourne, S.L.N. by the Pfizer Australia Research Fellowship, and L.W. by an NHMRC Fellowship. S.C, A. Dakic, and A. D'Amico designed and performed most of the experiments and provided input in the manuscript. S.H.M.P and K.T.G performed analysis of the Flt3 promoter. S.L.N and L.W supervised the experimental design, analyzed experiments, and cowrote the manuscript.