Transcription Factor PU.1 Promotes Conventional Dendritic Cell Identity and Function via Induction of Transcriptional Regulator DC-SCRIPT
Open accessAbstract
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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PU.1 is a master regulator of innate cell functionality.
“We hypothesized that the transcription factor PU.1, a master regulator of innate cell functionality, may augment pro-inflammatory CAR T cell activation.”
From Ectopic PU.1 Expression Provides Chimeric Antigen Receptor (CAR) T Cells with Innate Cell Capacities Including IFN-β Release (2024) · cites this paper as [10]
PU.1 facilitates the expression of genes governing the interface of innate and adaptive immunity, such as IFN-β, along with a variety of costimulatory receptors.
“Generally, PU.1 facilitates the expression of genes governing the interface of innate and adaptive immunity, such as IFN-β, along with a variety of costimulatory receptors [10,15].”
From Ectopic PU.1 Expression Provides Chimeric Antigen Receptor (CAR) T Cells with Innate Cell Capacities Including IFN-β Release (2024) · cites this paper as [10]
PU.1 controls antigen presentation and the induction of type-I interferon.
“PU.1 (Purine Rich Box-1) is a crucial key factor that also controls antigen presentation and the induction of type-I interferon [10].”
From Ectopic PU.1 Expression Provides Chimeric Antigen Receptor (CAR) T Cells with Innate Cell Capacities Including IFN-β Release (2024) · cites this paper as [10]
PU.1 upregulates costimulatory receptors such as CD80 and CD86.
“For upregulating costimulatory receptors, such as CD80 and CD86, PU.1 (Purine Rich Box-1) is a crucial key factor that also controls antigen presentation and the induction of type-I interferon [10].”
From Ectopic PU.1 Expression Provides Chimeric Antigen Receptor (CAR) T Cells with Innate Cell Capacities Including IFN-β Release (2024) · cites this paper as [10]
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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.
- ORCID
- 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
- bronze
- doi.org
- Licence
- 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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