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Cited by 106Immune Cell Function and InteractionT-cell and B-cell ImmunologyCytokine Signaling Pathways and Interactions

Differential Transcriptional Regulation of CD161 and a Novel Gene, 197/15a , by IL-2, IL-15, and IL-12 in NK and T Cells

Azzoni, Livio, Zatsepina, Olga, Abebe, Bekele, Bennett, Ian M, Kanakaraj, Palanisamy, Perussia, Bice·1998·The Journal of Immunology
DOI 10.4049/jimmunol.161.7.3493
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Abstract

Cytokine-mediated enhancement of spontaneous cytotoxicity depends, at least in part, on modulation of the expression of surface molecules responsible for recognition of target cell structures and triggering or inhibition of the cytotoxic machinery. We previously demonstrated that expression of transcription factors (e.g., Egr-1, JunB, and c-Fos) is differentially regulated by IL-2 and IL-12. Here we show that expression of CD161/NKR-P1A, a molecule involved in triggering cytotoxicity, is specifically up-regulated by IL-12. CD161 transcription, mRNA accumulation, and surface expression are increased by IL-12. Other cytokines sharing the IL-2R β- and/or common γ-chains (i.e., IL-15, IL-4, and IL-7) do not mediate these effects. In an effort to analyze the mechanisms by which IL-2, IL-12, and IL-15 differentially regulate gene transcription, we have isolated a novel gene, 197/15a, the expression of which in NK and T cells is down-regulated by IL-2 and IL-15, up-regulated by IL-12, and not affected by IL-4 and IL-7. IL-2 and IL-15 act, at least in part, repressing 197/15a transcription; their effect on 197/15a mRNA accumulation is partially independent of novel protein synthesis, likely not mediated by JunB, Bcl-2, or Bax, and requires the activity of rapamycin-sensitive molecule(s). The observation that IL-2 and IL-12 differentially modulate CD161 expression suggests the existence of cytokine-specific mechanisms of modulation of spontaneous cytotoxicity based on the regulation of expression of surface molecules involved in target cell recognition and/or triggering of the cytolytic machinery.

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Crossref · 10.4049/jimmunol.161.7.3493

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  • PDCD4 gene expression is post-transcriptionally downregulated by microenvironmental factors such as growth factors and interleukins.

    “PDCD4 gene mutations have not been found in tumor cells but gene expression was post transcriptionally downregulated by micro environmental factors such as growth factors and interleukins.”

    From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [8]

  • PDCD4 expression is modulated by interleukins such as IL-2, IL-12, and IL-15.

    “The expression of the gene was modulated by interleukins such as IL-2, IL-12, and IL-15 [8].”

    From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [8]

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Authors
Azzoni, L., Zatsepina, O., Abebe, B., Bennett, I. M., Kanakaraj, P., & Perussia, B.
Affiliations
  • Thomas Jefferson University (US)
  • Sidney Kimmel Cancer Center (US)
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
1998-10-01
Volume
161
Issue
7
Pages
3493-3500
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.161.7.3493
OpenAlex
W2098965772
Cited by
105
References
54
Citations by year
2026: 2 · 2025: 2 · 2024: 1 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 6 · 2018: 3 · 2017: 8 · 2016: 1 · 2015: 3 · 2014: 5 · 2013: 5 · 2012: 3
FWCI
0.96
Type
journal article
Language
en
Open access
closed
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ca037155-13, 5r01ca045284-11)
  • National Cancer Institute (T32CA09683, CA 45284, CA37155, T32CA009683)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
CD161, NKR-P1A, IL-12, interleukin-2, IL-15, natural killer cells, T cells, transcriptional regulation, spontaneous cytotoxicity, cytokine signaling, JunB, EGR1, c-fos, surface molecule expression
MeSH terms
Amino Acid Sequence, Animals, Antigens, Surface, Clone Cells, Cytotoxicity, Immunologic, Gene Expression Regulation, Humans, Interleukin-2, Interleukins, Killer Cells, Natural, Molecular Sequence Data, Proteins, Sequence Homology, Nucleic Acid, Transcription, Genetic, Protein Biosynthesis, Tumor Cells, Cultured, T-Lymphocyte Subsets, Cytokines, RNA-Binding Proteins, Receptors, Interleukin, Interleukin-12, Cell Cycle Proteins, Interleukin-15, Lectins, C-Type, Apoptosis Regulatory Proteins, Mice, NK Cell Lectin-Like Receptor Subfamily B

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