ArticleProceedings of the National Academy of Sciences of the United States of America2015
Opposing roles of STAT1 and STAT3 in IL-21 function in CD4+ T cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 121 citations in OpenAlex.
- TNF overproduction impairs epithelial staphylococcal response in hyper IgE syndrome.The Journal of clinical investigation · 2018Trial
- An IL-21R STAT hypomorph circumvents functional redundancy in germinal centre responses.eLife · 2026Article
- Regulation of follicular helper T cell subset differentiation in health and disease.Journal of molecular medicine (Berlin, Germany) · 2026Review
- USP9X regulates copper-induced CASP9/CASP3/GSDME-dependent pyroptosis by deubiquitinating JAK1.Apoptosis : an international journal on programmed cell death · 2026Article
- A Literature Review of Interleukins in the Development and Treatment of Breast Cancer.International journal of molecular sciences · 2026Review
- DOCK8 and STAT3 cooperate to restrain IgE-inducing T follicular helper cells.The Journal of experimental medicine · 2026Article
- Aberrant STAT3 activation and overproduction of IL-21 in systemic lupus erythematosus: role of miR-155 and miR-21 in target genesFrontiers in immunology · 2026Article
- Alleviation of experimental arthritis in SKG mice throughFrontiers in immunology · 2026Article
- Engineering IL-21 secretion in T cells using druggable ligand-responsive stabilized domains.Scientific reports · 2025Article
- Review
- STAT Signature Dish: Serving Immunity with a Side of Dietary Control.Biomolecules · 2025Review
- Defining a novel DYRK1A-gp130/IL-6R-pSTAT axis that regulates Th17 differentiation.ImmunoHorizons · 2025Article
- Sex-specific impact of B cell-derived IL-10 on tuberculosis resistance.Frontiers in immunology · 2025Article
- JAK-STAT pathway, type I/II cytokines, and new potential therapeutic strategy for autoimmune bullous diseases: update on pemphigus vulgaris and bullous pemphigoid.Frontiers in immunology · 2025Review
- The genetics of hyper IgE syndromes.Frontiers in immunology · 2025Review
- Glioblastoma induces the recruitment and differentiation of dendritic-like "hybrid" neutrophils from skull bone marrow.Cancer cell · 2024Article
- LIM-domain-only 4 (LMO4) enhances CD8Signal transduction and targeted therapy · 2024Article
- Network meta-analysis of the molecular mechanisms and signaling pathways underlying alcohol-induced thymic atrophy.Alcohol, clinical & experimental research · 2024Article
- Immunomodulatory effects of Diospyros peregrina fruit preparation (DFP) in non-small cell lung cancer (NSCLC) by utilizing dendritic cell-mediated antigen presentation and T helper (TH) cell differentiation.Medical oncology (Northwood, London, England) · 2024Article
- IL-17 and IL-21: Their Immunobiology and Therapeutic Potentials.Immune network · 2024Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
IL-21 is a type I cytokine essential for immune cell differentiation and function. Although IL-21 can activate several STAT family transcription factors, previous studies focused mainly on the role of STAT3 in IL-21 signaling. Here, we investigated the role of STAT1 and show that STAT1 and STAT3 have at least partially opposing roles in IL-21 signaling in CD4(+) T cells. IL-21 induced STAT1 phosphorylation, and this was augmented in Stat3-deficient CD4(+) T cells. RNA-Seq analysis of CD4(+) T cells from Stat1- and Stat3-deficient mice revealed that both STAT1 and STAT3 are critical for IL-21-mediated gene regulation. Expression of some genes, including Tbx21 and Ifng, was differentially regulated by STAT1 and STAT3. Moreover, opposing actions of STAT1 and STAT3 on IFN-γ expression in CD4(+) T cells were demonstrated in vivo during chronic lymphocytic choriomeningitis infection. Finally, IL-21-mediated induction of STAT1 phosphorylation, as well as IFNG and TBX21 expression, were higher in CD4(+) T cells from patients with autosomal dominant hyper-IgE syndrome, which is caused by STAT3 deficiency, as well as in cells from STAT1 gain-of-function patients. These data indicate an interplay between STAT1 and STAT3 in fine-tuning IL-21 actions.
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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.