PU.1 Expression Delineates Heterogeneity in Primary Th2 Cells
Open accessAbstract
Primary T helper 2 cells are heterogeneous, expressing subsets of cytokines at varying levels. Mechanisms controlling this spectrum of phenotypes are still unclear. The ETS family transcription factor PU.1 is expressed in Th2 but not Th1 cells. Th2 cytokine production is decreased in cultures transduced with a PU.1-expressing retrovirus and increased in Th2 cells following RNAi that decreases PU.1 expression. In primary cultures, PU.1 expression is restricted to a subpopulation of Th2 cells that express CCL22 and a subset of Th2 cytokines. PU.1 regulates the Th2 phenotype by interfering with GATA-3 DNA binding without altering GATA-3 protein levels. Thus, the expression of PU.1 in subsets of Th2 cells establishes a defined cytokine profile and contributes towards establishing the spectrum of cytokine production observed in Th2 populations.
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PU.1 functions, at least in part, by limiting the ability of GATA-3 and IRF4 to interact with cytokine loci targets.
“PU.1 functions, at least in part, by limiting the ability of GATA-3 and IRF4 to interact with cytokine loci targets7–9.”
From The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation (2010) · cites this paper as [8]
The Results report reduced GATA-3 binding to the IL-4 enhancer in IL-4-low Th2 cells, and the Discussion says PU.1 functions partly by interfering with GATA-3 DNA binding. The cited paper does not establish the corresponding claim about IRF4; a search for IRF4 and cytokine-locus targets found no supporting passage. Page numbers were not available in our copy. (LLM, conf=0.89)
Experimental — accuracy not yet measuredDecreasing PU.1 expression or PU.1-deficiency increases overall cytokine production specifically in populations of cells that secrete two or more cytokines.
“while shRNA that decreased PU.1 expression, or PU.1-deficiency, increased overall cytokine production specifically in populations of cells that secreted two or more cytokines7,8.”
From The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation (2010) · cites this paper as [8]
The Results section reports that PU.1 shRNA increased IL-4, IL-5, and IL-10 production, with the largest increases in cells positive for both IL-4 and IL-5 or both IL-4 and IL-10. But the same passage says the authors could not examine mature PU.1-deficient T cells; this paper therefore does not establish the deficiency part of the claim. (LLM, conf=0.90)
Experimental — accuracy not yet measuredPU.1 appears to have distinct effects in various types of T cells: negatively regulating γδ T cell numbers, negatively regulating Th2 cytokine production and TCR expression, while promoting IL-9 expression.
“Thus, PU.1 appears to have distinct effects in various types of T cells, negatively regulating γδ T cell numbers, negatively regulating Th2 cytokine production and TCR expression, while promoting IL-9 expression [15]–[17].”
From The Transcription Factor PU.1 Regulates γδ T Cell Homeostasis (2011) · cites this paper as [16]
The Results (page not provided) report that PU.1 expression decreased Th2 cytokines, including IL-4, IL-5, IL-10, and IL-13. Our copy does not establish the attributed effects on γδ T cell numbers, TCR expression, or IL-9 expression. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPU.1 expression in T cells and subpopulations of Th2 cells contributes to heterogeneity in Th2 cytokine expression and TCR expression.
“However the expression of PU.1 in T cells and subpopulations of Th2 cells contributes to heterogeneity in Th2 cytokine expression and TCR expression [16].”
From The Transcription Factor PU.1 Regulates γδ T Cell Homeostasis (2011) · cites this paper as [16]
The Results and Discussion (pages unavailable) show that PU.1 is expressed in a subset of Th2 cells and contributes to variation in their cytokine profiles. They do not show that PU.1 contributes to heterogeneity in TCR expression; the paper’s references to anti-CD3 stimulation do not establish that point. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPU.1 is specifically expressed in subpopulations of TH2 cells that have low IL-4 expression.
“PU.1 was specifically expressed in subpopulations of TH2 cells that had low IL-4 expression.”
From The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation (2010) · cites this paper as [8]
Ectopic expression of PU.1 reduces production of most TH2 cytokines.
“Ectopic expression of PU.1 reduced production of most TH2 cytokines”
From The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation (2010) · cites this paper as [8]
PU.1 limits expression of Th2 cytokines and contributes to Th2 heterogeneity.
“We have also demonstrated that PU.1 limits the expression of Th2 cytokines and contributes to Th2 heterogeneity [15], [16].”
From The Transcription Factor PU.1 Regulates γδ T Cell Homeostasis (2011) · cites this paper as [16]
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References 50 · Cited by 159
Research works printed but not linked: 22
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- Authors
- Chang, H.-C., Zhang, S., Thieu, V. T., Slee, R. B., Bruns, H. A., Laribee, R. N., Klemsz, M. J., & Kaplan, M. H.
- Affiliations
- Walther Cancer Foundation (US)
- Corresponding author
- Kaplan, Mark H.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2005-06
- Volume
- 22
- Issue
- 6
- Pages
- 693-703
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2056835764
- Cited by
- 159
- References
- 50
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 7 · 2023: 8 · 2022: 4 · 2021: 4 · 2020: 9 · 2019: 5 · 2018: 10 · 2017: 8 · 2016: 7 · 2015: 12 · 2014: 6 · 2013: 16 · 2012: 7
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3004 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI-45515, AI57459, R01AI057459)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007519, DK007519)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- PU.1, Th2 cells, cytokine production, GATA3, CCL22, ETS transcription factors, transcriptional regulation, primary T cells
- MeSH terms
- Proto-Oncogene Protein Spi-1, Animals, Cells, Cultured, DNA-Binding Proteins, Female, Flow Cytometry, Mice, Inbred BALB C, Phenotype, Proto-Oncogene Proteins, Retroviridae, Blotting, Northern, Blotting, Western, Trans-Activators, Cytokines, Th1 Cells, Th2 Cells, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, Immunoprecipitation, GATA3 Transcription Factor, Mice
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