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Cited by 41Tuberculosis Research and EpidemiologyT-cell and B-cell ImmunologyGenomics and Chromatin Dynamics

The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.

Cyclic AMP Response Element-Binding Protein Positively Regulates Production of IFN-γ by T Cells in Response to a Microbial Pathogen

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Samten, Buka, Howard, Susan T, Weis, Steven E, Wu, Shiping, Shams, Homayoun, Townsend, James C, Safi, Hassan, Barnes, Peter F·2005·The Journal of Immunology
DOI 10.4049/jimmunol.174.10.6357
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Abstract

IFN-γ is essential for resistance to many intracellular pathogens, including Mycobacterium tuberculosis. Transcription of the IFN-γ gene in activated T cells is controlled by the proximal promoter element (−73 to −48 bp). CREB binds to the IFN-γ proximal promoter, and binding is enhanced by phosphorylation of CREB. Studies in human T cell lines and in transgenic mice have yielded conflicting results about whether CREB is a positive or a negative regulator of IFN-γ transcription. To determine the role of CREB in mediating IFN-γ production in response to a microbial pathogen, we evaluated the peripheral blood T cell response to M. tuberculosis in healthy tuberculin reactors. EMSAs, chromatin immunoprecipitation, and Western blotting demonstrated that stimulation of PBMC with M. tuberculosis induced phosphorylation and enhanced binding of CREB to the IFN-γ proximal promoter. Neutralization of CREB with intracellular Abs or down-regulation of CREB levels with small interfering RNA decreased M. tuberculosis-induced production of IFN-γ and IFN-γ mRNA expression. In addition, M. tuberculosis-stimulated T cells from tuberculosis patients, who have ineffective immunity, showed diminished IFN-γ production, reduced amounts of CREB binding to the IFN-γ proximal promoter, and absence of phosphorylated CREB. These findings demonstrate that CREB positively regulates IFN-γ production by human T cells that respond to M. tuberculosis.

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  • Transcription factor enrichment analysis revealed that formate-induced transcriptional changes were linked with enrichment in transcription factors regulating proliferation and metabolism, effector function, and differentiation and epigenetic control.

    “Transcription factor enrichment analysis73 revealed that formate-induced transcriptional changes were linked with an enrichment in transcription factors regulating proliferation and metabolism (e.g.: Myc, Max, Myb)74, effector function (e.g.: Fos, Rela, Stat1, Cebpb)75–77 as well as differentiation and epigenetic control (e.g.: Ets1, Yy1, Pou2f2)78 (Figure 6M).”

    From Exercise-induced microbiota metabolite enhances CD8 T cell antitumor immunity promoting immunotherapy efficacy (2025) · cites this paper as [75]

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Metadata

Authors
Samten, B., Howard, S. T., Weis, S. E., Wu, S., Shams, H., Townsend, J. C., Safi, H., & Barnes, P. F.
Affiliations
  • The University of Texas Health Science Center at Tyler (US)
  • University of North Texas (US)
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2005-05
Volume
174
Issue
10
Pages
6357-6363
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.174.10.6357
OpenAlex
W1519377554
Cited by
41
References
33
Citations by year
2025: 1 · 2023: 4 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 1 · 2015: 1 · 2013: 2 · 2012: 2
FWCI
1.92
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)
Funders
  • Cain Foundation
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (AI44935, R01AI044935)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • 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
CREB, interferon-gamma, T cell activation, Mycobacterium tuberculosis, CREB phosphorylation, transcriptional regulation, tuberculosis, intracellular pathogens, tuberculin reactors, IFN-γ mRNA expression
MeSH terms
Cells, Cultured, Humans, Interferon-gamma, Intracellular Fluid, Leukocytes, Mononuclear, Mycobacterium tuberculosis, Nuclear Proteins, Phosphorylation, Promoter Regions, Genetic, Protein Binding, RNA, Messenger, Serine, T-Lymphocytes, Trans-Activators, Down-Regulation, Up-Regulation, Cyclic AMP Response Element-Binding Protein, RNA, Small Interfering, CREB-Binding Protein

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