Cited by 104Immunotherapy and Immune ResponsesT-cell and B-cell ImmunologyGenomics and Chromatin Dynamics

Transcription Factor PU.1 Promotes Conventional Dendritic Cell Identity and Function via Induction of Transcriptional Regulator DC-SCRIPT

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Chopin, Michaël, Lun, Aaron T., Zhan, Yifan, Schreuder, Jaring, Coughlan, Hannah, D’Amico, Angela, Mielke, Lisa A., Almeida, Francisca F. +10 more·2019·Immunity

Abstract

Dendritic cells (DCs) are can be broadly divided into conventional (cDC) and plasmacytoid (pDC) subsets. Despite the importance of this lineage diversity, its genetic basis is not fully understood. We found that conditional ablation of the Ets-family transcription factor PU.1 in DC-restricted progenitors led to increased pDC production at the expense of cDCs. PU.1 controlled many of the cardinal functions of DCs, such as antigen presentation by cDCs and type I interferon production by pDCs. Conditional ablation of PU.1 de-repressed the pDC transcriptional signature in cDCs. The combination of genome-wide mapping of PU.1 binding and gene expression analysis revealed a key role for PU.1 in maintaining cDC identity through the induction of the transcriptional regulator DC-SCRIPT. PU.1 activated DC-SCRIPT expression, which in turn promoted cDC formation, particularly of cDC1s, and repressed pDC development. Thus, cDC identity is regulated by a transcriptional node requiring PU.1 and DC-SCRIPT.

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Crossref · 10.1016/j.immuni.2018.11.010

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Authors
Chopin, M., Lun, A. T., Zhan, Y., Schreuder, J., Coughlan, H., D’Amico, A., Mielke, L. A., Almeida, F. F., Kueh, A. J., Dickins, R. A., Belz, G. T., Naik, S. H., Lew, A. M., Bouillet, P., Herold, M. J., Smyth, G. K., Corcoran, L. M., & Nutt, S. L.
Affiliations
  • The University of Melbourne (AU)
  • Monash University (AU)
Corresponding author
  • Chopin, Michaël
  • Nutt, Stephen L.
Venue
Immunity
Publisher
Elsevier BV
Published
2019-01
Volume
50
Issue
1
Pages
77-90.e5
ISSN
1074-7613 (ISSN-L)
OpenAlex
W2908480177
Cited by
104
References
63
Citations by year
2026: 15 · 2025: 16 · 2024: 19 · 2023: 10 · 2022: 15 · 2021: 14 · 2020: 11 · 2019: 4
FWCI
4.41
Type
journal article
Language
en
Open access
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Health and Medical Research Council of Australia (5575500, 1054925, 1048278, 1054618, 1058892, 1037321, 1043414, 1080321, 1105209)
  • Cancer Council Victoria Venture Grant and Victorian Cancer Agency (TRP13041)
  • Australian Phenomics Network
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 › Genomics and Chromatin Dynamics
Keywords
PU.1, myeloid dendritic cells, plasmacytoid dendritic cells, ETS transcription factors, antigen presentation, type I interferon, cDC1, transcriptional regulation, conditional gene deletion
MeSH terms
Proto-Oncogene Protein Spi-1, Animals, Cell Differentiation, Dendritic Cells, DNA-Binding Proteins, Gene Expression Regulation, Humans, Interferon Type I, Mice, Transgenic, Nuclear Proteins, Proto-Oncogene Proteins, Transcription Factors, Signal Transduction, Trans-Activators, Antigen Presentation, Cell Lineage, Mice, HEK293 Cells, Transcriptome

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