ArticleThe Journal of experimental medicine2000
Transient inhibition of interleukin 4 signaling by T cell receptor ligation.
Article in The Journal of experimental medicine, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 58 citations in OpenAlex.
- Integrated Clinical Trial and Molecular Profiling Reveals Immune Drivers of Chronic Hand Eczema.Allergy · 2026Trial
- Recent advances in understanding the role of IL-4 signaling.Faculty reviews · 2021Review
- Seventeen-Year Journey Working With a Master.Frontiers in immunology · 2018Article
- Ndfip-mediated degradation of Jak1 tunes cytokine signalling to limit expansion of CD4+ effector T cells.Nature communications · 2016Article
- The common γ-chain cytokine receptor: tricks-and-treats for T cells.Cellular and molecular life sciences : CMLS · 2016Review
- Avidity of human T cell receptor engineered CD4(+) T cells drives T-helper differentiation fate.Cellular immunology · 2016Article
- Review
- Thymic low affinity/avidity interaction selects natural Th1 cells.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- The signaling symphony: T cell receptor tunes cytokine-mediated T cell differentiation.Journal of leukocyte biology · 2015Review
- T cell receptor stimulation impairs IL-7 receptor signaling by inducing expression of the microRNA miR-17 to target Janus kinase 1.Science signaling · 2014Article
- ITK tunes IL-4-induced development of innate memory CD8+ T cells in a γδ T and invariant NKT cell-independent manner.Journal of leukocyte biology · 2014Article
- Forskolin-inducible cAMP pathway negatively regulates T-cell proliferation by uncoupling the interleukin-2 receptor complex.The Journal of biological chemistry · 2013Article
- IL-7 signaling must be intermittent, not continuous, during CD8⁺ T cell homeostasis to promote cell survival instead of cell death.Nature immunology · 2013Article
- Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors.Immunological reviews · 2010Review
- Signaling by intrathymic cytokines, not T cell antigen receptors, specifies CD8 lineage choice and promotes the differentiation of cytotoxic-lineage T cells.Nature immunology · 2010Article
- Differentiation of effector CD4 T cell populations (*).Annual review of immunology · 2010Review
- Control of T helper cell differentiation through cytokine receptor inclusion in the immunological synapse.The Journal of experimental medicine · 2009Article
- Cross-regulation of signaling by ITAM-associated receptors.Nature immunology · 2009Review
- Integration of cytokine and heterologous receptor signaling pathways.Nature immunology · 2009Review
- A signal-switch hypothesis for cross-regulation of cytokine and TLR signalling pathways.Nature reviews. Immunology · 2008Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Interleukin (IL)-4 and IL-12 together with T cell receptor (TCR) engagement are crucial for the differentiation of CD4(+) T cells into T helper (Th)2 or Th1 cells, respectively. Although IL-4 receptors (IL-4Rs) but not IL-12Rs are expressed on naive CD4(+) T cells, IL-4 has no apparent advantage over IL-12 in driving naive T cell differentiation when the cells are primed with both IL-4 and IL-12 in vitro. It was found that IL-4-induced phosphorylation of Janus kinases 1 and 3, IL-4R alpha, signal transducer and activator of transcription 6, and insulin receptor substrate 2 was strikingly but transiently inhibited by TCR ligation both in conventional and TCR transgenic T cells. TCR engagement also blocked the expression of an IL-4-inducible gene. Signals induced by other cytokines, including IL-2, IL-6, and interferon alpha, but not by insulin-like growth factor 1, were also blocked by TCR engagement. The capacity of various inhibitors to reverse TCR-mediated inhibition of IL-4 signaling suggested that activation of the Ras-mitogen-activated protein kinase pathway and of the calcineurin pathway contribute to desensitizing IL-4R. IL-4 responsiveness returned at about the time ( approximately 12 h) that IL-12-mediated signaling was first observed. Thus, through different mechanisms, neither IL-4R nor IL-12R has any clear advantage in polarizing cells; rather, the availability of cytokine is probably the limiting factor in this process.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.