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Cited by 137T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisGenomics and Chromatin Dynamics

IFN Regulatory Factor 4 Regulates the Expression of a Subset of Th2 Cytokines

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Ahyi, Ayele-Nati N, Chang, Hua-Chen, Dent, Alexander L, Nutt, Stephen L, Kaplan, Mark H·2009·The Journal of Immunology
DOI 10.4049/jimmunol.0803302PMC PMC2734910
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Abstract

Th2 cells can be subdivided into subpopulations depending on the level of a cytokine and the subsets of cytokines they produce. We have recently identified the ETS family transcription factor PU.1 as regulating heterogeneity in Th2 populations. To define additional factors that might contribute to Th2 heterogeneity, we examined the PU.1 interacting protein IFN-regulatory factor (IRF)4. When Th2 cells are separated based on levels of IL-10 secretion, IRF4 expression segregates into the subset of Th2 cells expressing high levels of IL-10. Infection of total Th2 cells, and IL-10 nonsecreting cells, with retrovirus-expressing IRF4, resulted in increased IL-4 and IL-10 expression, no change in IL-5 or IL-13 production and decreased Il9 transcription. Transfection of an IRF4-specific small interfering RNA into Th2 cells decreases IL-10 production. IRF4 directly binds the Il10 gene as evidenced by chromatin immunoprecipitation assay, and regulates Il10 control elements in a reporter assay. IRF4 interacts with PU.1, and in PU.1-deficient T cells there was an increase in IRF4 binding to the Il10 gene, and in the ability of IRF4 to induce IL-10 production compared with wild-type cells and Il10 promoter activity in a reporter assay. Further heterogeneity of IRF4 expression was observed in Th2 cells analyzed for expression of multiple Th2 cytokines. Thus, IRF4 promotes the expression of a subset of Th2 cytokines and contributes to Th2 heterogeneity.

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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 [9]

    The Results section, “Functional interactions of PU.1 and IRF4” (page unavailable), reports greater IRF4 binding at the Il10 promoter in PU.1-deficient Th2 cells, with a similar trend at the Il4 promoter. It also shows that PU.1 interacts with GATA-3, but does not show that PU.1 limits GATA-3 binding to cytokine loci. (LLM, conf=0.87)

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Authors
Ahyi, A.-N. N., Chang, H.-C., Dent, A. L., Nutt, S. L., & Kaplan, M. H.
Affiliations
  • Indiana University Indianapolis (US)
  • Department of Pediatrics, Herman B. Wells Center for Pediatric Research
  • Walter and Eliza Hall Institute of Medical Research (AU)
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2009-08-01
Volume
183
Issue
3
Pages
1598-1606
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.0803302
PMC
PMC2734910
OpenAlex
W2123298166
Cited by
137
References
7
Citations by year
2026: 1 · 2025: 4 · 2024: 5 · 2023: 5 · 2022: 5 · 2021: 5 · 2020: 9 · 2019: 8 · 2018: 6 · 2017: 10 · 2016: 7 · 2015: 8 · 2014: 14 · 2013: 17 · 2012: 9
FWCI
4.75
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
Funders
National Institute of Allergy and Infectious Diseases (AI057459, R01AI057459)
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
Th2 cells, IL-10, IL-4, IL-13, IL-5, IL-9, PU.1, ETS transcription factors, cytokine gene regulation, transcriptional regulation, T cell subsets
MeSH terms
Interferon Regulatory Factor-4, Proto-Oncogene Protein Spi-1, Animals, Gene Expression Regulation, Protein Binding, Proto-Oncogene Proteins, Trans-Activators, Cytokines, Interleukin-10, Th2 Cells, Interferon Regulatory Factors, Mice

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