Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice
Abstract
Interactions between cytokine and receptor lead to the activation of multiple signalling molecules, including the family of signal transducer and activator of transcription (STAT) proteins. STAT4 is one member of this family, and is activated only in response to the cytokine interleukin (IL)-12 (refs 5, 6). By gene targeting, we have generated mice deficient in STAT4 to determine whether the function of this transcription factor is redundant with other signalling molecules activated by IL-12. IL-12-induced increases in the production of interferon (IFN)-gamma cellular proliferation and natural killer (NK) cell cytotoxicity are abrogated in lymphocytes from STAT4-deficient mice. The development of Th1 cells in response to either IL-12 of Listeria monocytogenes is also impaired in the absence of Stat4. Furthermore, Stat4-deficient lymphocytes demonstrate a propensity towards the development of Th2 cells. These results demonstrate that Stat4 is essential for mediating responses to IL-12 in lymphocytes, and regulating the differentiation of both Th1 and Th2 cells.
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All of the other STAT knock-outs have relatively mild phenotypes correlated with rather specific defects in response to certain cytokines or growth factors.
“All of the other STAT knock-outs have relatively mild phenotypes correlated with rather specific defects in response to certain cytokines or growth factors (12”
From STAT3 Contributes to the Mitogenic Response of Hepatocytes during Liver Regeneration (2002) · cites this paper as [34]
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- Authors
- Kaplan, M. H., Sun, Y.-L., Hoey, T., & Grusby, M. J.
- Affiliations
- Harvard University (US)
- Venue
- Nature
- Published
- 1996-07
- Volume
- 382
- Issue
- 6587
- Pages
- 174-177
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2012628280
- Cited by
- 1,240
- References
- 1
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 9 · 2023: 17 · 2022: 17 · 2021: 13 · 2020: 25 · 2019: 21 · 2018: 12 · 2017: 26 · 2016: 18 · 2015: 32 · 2014: 39 · 2013: 39 · 2012: 29
- FWCI
- 33.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- STAT4, IL-12, Th1 differentiation, Th2 differentiation, interferon-gamma, NK cell cytotoxicity, Listeria monocytogenes, cytokine signaling, transcription factors, lymphocyte proliferation
- MeSH terms
- Animals, Cell Differentiation, Cell Line, Cells, Cultured, Cytotoxicity, Immunologic, DNA-Binding Proteins, Interferon-gamma, Killer Cells, Natural, Listeria monocytogenes, Lymphocyte Activation, Mice, Inbred BALB C, Mutation, Spleen, Signal Transduction, Trans-Activators, Gene Targeting, Th1 Cells, Th2 Cells, Interleukin-12, STAT4 Transcription Factor, Mice
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