Cited by 279Immunotherapy and Immune ResponsesT-cell and B-cell ImmunologyDevelopmental Biology and Gene Regulation

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

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Carotta, Sebastian, Dakic, Aleksandar, D'Amico, Angela, Pang, Swee Heng Milon, Greig, Kylie T., Nutt, Stephen L., Wu, Li·2010·Immunity

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 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.

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Crossref · 10.1016/j.immuni.2010.05.005

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  • PU.1 is directly required to maintain expression of Flt3, which is indispensable for progenitors with B and T cell potentials.

    “PU.1 is directly required to maintain the expression of the cytokine receptor Flt3 that is indispensable for progenitors with B and T cell potentials (73).”

    From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [73]

    The Discussion (page unavailable) states that PU.1 has an essential, direct role in regulating Flt3 expression in multipotent hematopoietic precursors and maintains its expression in formed dendritic cells. It says Flt3 plays an important role in lymphoid-primed multipotent and common lymphoid progenitors, but does not establish that Flt3 is indispensable for progenitors with B- and T-cell potential. (LLM, conf=0.84)

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Authors
Carotta, S., Dakic, A., D'Amico, A., Pang, S. H. M., Greig, K. T., Nutt, S. L., & Wu, L.
Affiliations
  • Walter and Eliza Hall Institute of Medical Research (AU)
  • The University of Melbourne (AU)
Corresponding author
  • Nutt, Stephen L.
  • Wu, Li
Venue
Immunity
Publisher
Elsevier BV
Published
2010-05
Volume
32
Issue
5
Pages
628-641
ISSN
1074-7613 (ISSN-L)
OpenAlex
W1963617750
Cited by
279
References
53
Citations by year
2026: 12 · 2025: 4 · 2024: 14 · 2023: 8 · 2022: 10 · 2021: 13 · 2020: 19 · 2019: 15 · 2018: 16 · 2017: 18 · 2016: 15 · 2015: 23 · 2014: 22 · 2013: 29 · 2012: 27
FWCI
12.38
Type
journal article
Language
en
Open access
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Leukaemia Foundation
  • University of Melbourne
  • Australian Research Council
  • National Health and Medical Research Council
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
PU.1, dendritic cell development, FLT3, Flt3 ligand, plasmacytoid dendritic cells, myeloid dendritic cells, GM-CSF, transcriptional regulation, dose-dependent gene expression, conditional gene deletion, hematopoietic progenitor cells
MeSH terms
Proto-Oncogene Protein Spi-1, Animals, Base Sequence, Cell Differentiation, Cells, Cultured, Dendritic Cells, Dose-Response Relationship, Drug, Flow Cytometry, Membrane Proteins, Mice, Transgenic, Molecular Sequence Data, Promoter Regions, Genetic, Proto-Oncogene Proteins, Trans-Activators, Polymerase Chain Reaction, Models, Immunological, Mice

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