ArticleThe Journal of experimental medicine2000
T cell receptor-induced calcineurin activation regulates T helper type 2 cell development by modifying the interleukin 4 receptor signaling complex.
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 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- Genetic Influences on Patient-Oriented Outcomes in Traumatic Brain Injury: A Living Systematic Review of Non-Apolipoprotein E Single-Nucleotide Polymorphisms.Journal of neurotrauma · 2021Pooled it
- Calcineurin in development and disease.Genes & diseases · 2022Review
- Blood Transcriptome Profiling Links Immunity to Disease Severity in Myotonic Dystrophy Type 1 (DM1).International journal of molecular sciences · 2022Article
- Tuning T helper cell differentiation by ITK.Biochemical Society transactions · 2020Review
- Regulation of T Helper Cell Fate by TCR Signal Strength.Frontiers in immunology · 2020Review
- Changes in DNA Methylation from Age 18 to Pregnancy in Type 1, 2, and 17 T Helper and Regulatory T-Cells Pathway Genes.International journal of molecular sciences · 2018Article
- A Natural Variant of the T Cell Receptor-Signaling Molecule Vav1 Reduces Both Effector T Cell Functions and Susceptibility to Neuroinflammation.PLoS genetics · 2016Article
- Current knowledge on psoriasis and autoimmune diseases.Psoriasis (Auckland, N.Z.) · 2016Review
- The signaling symphony: T cell receptor tunes cytokine-mediated T cell differentiation.Journal of leukocyte biology · 2015Review
- Effect of infliximab on acute hepatic ischemia/reperfusion injury in rats.International journal of clinical and experimental medicine · 2015Article
- 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
- CD4+ T cell subset differentiation and avidity setpoint are dictated by the interplay of cytokine and antigen mediated signals.PloS one · 2014Article
- Effects of sugammadex on immunoreactivity of calcineurin in rat testes cells after neuromuscular block: a pilot study.Journal of molecular histology · 2012Article
- Coreceptor gene imprinting governs thymocyte lineage fate.The EMBO journal · 2012Article
- Increased expression of IRF4 and ETS1 in CD4+ cells from patients with intermittent allergic rhinitis.Allergy · 2012Article
- Costimulator B7-DC attenuates strong Th2 responses induced by Nippostrongylus brasiliensis.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- Red blood cells carry out T cell growth and survival bioactivities that are sensitive to cyclosporine A.Cellular and molecular life sciences : CMLS · 2009Article
- Lymphoid enhancer factor interacts with GATA-3 and controls its function in T helper type 2 cells.Immunology · 2008Article
- Gfi1-mediated stabilization of GATA3 protein is required for Th2 cell differentiation.The Journal of biological chemistry · 2008Article
- Signals from OX40 regulate nuclear factor of activated T cells c1 and T cell helper 2 lineage commitment.Proceedings of the National Academy of Sciences of the United States of America · 2006Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The activation of downstream signaling pathways of both T cell receptor (TCR) and interleukin 4 receptor (IL-4R) is essential for T helper type 2 (Th2) cell development, which is central to understanding immune responses against helminthic parasites and in allergic and autoimmune diseases. However, little is known about how these two distinct signaling pathways cooperate with each other to induce Th2 cells. Here, we show that successful Th2 cell development depends on the effectiveness of TCR-induced activation of calcineurin. An inhibitor of calcineurin activation, FK506, inhibited the in vitro anti-TCR-induced Th2 cell generation in a dose-dependent manner. Furthermore, the development of Th2 cells was significantly impaired in naive T cells from dominant-negative calcineurin Aalpha transgenic mice, whereas that of Th1 cells was less affected. Efficient calcineurin activation in naive T cells upregulated Janus kinase (Jak)3 transcription and the amount of protein. The generation of Th2 cells induced in vitro by anti-TCR stimulation was inhibited significantly by the presence of Jak3 antisense oligonucleotides, suggesting that the Jak3 upregulation is an important event for the Th2 cell development. Interestingly, signal transducer and activator of transcription (STAT)5 became physically and functionally associated with the IL-4R in the anti-TCR-activated developing Th2 cells that received efficient calcineurin activation, and also in established cloned Th2 cells. In either cell population, the inhibition of STAT5 activation resulted in a diminished IL-4-induced proliferation. Moreover, our results suggest that IL-4-induced STAT5 activation is required for the expansion process of developing Th2 cells. Thus, Th2 cell development is controlled by TCR-mediated activation of the Ca(2+)/calcineurin pathway, at least in part, by modifying the functional structure of the IL-4R signaling complex.
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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.