ArticleThe Journal of allergy and clinical immunology2013
Signal transducer and activator of transcription 3 (STAT3) mutations underlying autosomal dominant hyper-IgE syndrome impair human CD8(+) T-cell memory formation and function.
Article in The Journal of allergy and clinical immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Pooled it
- Primary atopic disorders: Monogenic insights into immunity.Journal of human immunity · 2026Review
- Metagenomic next-generation sequencing: a game-changer in the diagnosis of unique intraocular infections.Eye (London, England) · 2025Article
- The genetics of hyper IgE syndromes.Frontiers in immunology · 2025Review
- Inherited human ZNF341 deficiency.Current opinion in immunology · 2023Review
- The ups and downs of STAT3 function: too much, too little and human immune dysregulation.Clinical and experimental immunology · 2023Review
- DisseminatedOpen forum infectious diseases · 2023Article
- STAT3 Role in T-Cell Memory Formation.International journal of molecular sciences · 2022Review
- Intrinsic Defects in B Cell Development and Differentiation, T Cell Exhaustion and Altered Unconventional T Cell Generation Characterize Human Adenosine Deaminase Type 2 Deficiency.Journal of clinical immunology · 2021Article
- Induction of Unique STAT Heterodimers by IL-21 Provokes IL-1RI Expression on CD8Immune network · 2021Article
- Genomic Spectrum and Phenotypic Heterogeneity of Human IL-21 Receptor Deficiency.Journal of clinical immunology · 2021Article
- STAT3 Hyper-IgE Syndrome-an Update and Unanswered Questions.Journal of clinical immunology · 2021Review
- Histone Deacetylase Inhibitors and IL21 Cooperate to Reprogram Human Effector CD8Cancer immunology research · 2020Article
- TCDD-mediated suppression of naïve human B cell IgM secretion involves aryl hydrocarbon receptor-mediated reduction in STAT3 serine 727 phosphorylation and is restored by interferon-γ.Cellular signalling · 2020Article
- On Two Cases with Autosomal Dominant Hyper IgE Syndrome: Importance of Immunological Parameters for Clinical Course and Follow-Up.Case reports in immunology · 2020Article
- The clinical, immunological and genetic features of 12 Chinese patients with STAT3 mutations.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2020Article
- Respiratory syncytial virus reduces STAT3 phosphorylation in human memory CD8 T cells stimulated with IL-21.Scientific reports · 2019Article
- Review
- A deep intronic splice mutation ofProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Stand by me(mory): Chronic infection diminishes memory pool via IL-6/STAT1.The Journal of experimental medicine · 2019Article
Corrections and comments
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Authors and funding
27 authors at 18 institutions in 7 countries.
Funding
Abstract
backgroundThe capacity of CD8(+) T cells to control infections and mediate antitumor immunity requires the development and survival of effector and memory cells. IL-21 has emerged as a potent inducer of CD8(+) T-cell effector function and memory development in mouse models of infectious disease. However, the role of IL-21 and associated signaling pathways in protective CD8(+) T-cell immunity in human subjects is unknown.
objectiveWe sought to determine which signaling pathways mediate the effects of IL-21 on human CD8(+) T cells and whether defects in these pathways contribute to disease pathogenesis in patients with primary immunodeficiencies caused by mutations in components of the IL-21 signaling cascade.
methodsHuman primary immunodeficiencies resulting from monogenic mutations provide a unique opportunity to assess the requirement for particular molecules in regulating human lymphocyte function. Lymphocytes from patients with loss-of-function mutations in signal transducer and activator of transcription 1 (STAT1), STAT3, or IL-21 receptor (IL21R) were used to assess the respective roles of these genes in human CD8(+) T-cell differentiation in vivo and in vitro.
resultsMutations in STAT3 and IL21R, but not STAT1, led to a decrease in multiple memory CD8(+) T-cell subsets in vivo, indicating that STAT3 signaling, possibly downstream of IL-21R, regulates the memory cell pool. Furthermore, STAT3 was important for inducing the lytic machinery in IL-21-stimulated naive CD8(+) T cells. However, this defect was overcome by T-cell receptor engagement.
conclusionThe IL-21R/STAT3 pathway is required for many aspects of human CD8(+) T-cell behavior but in some cases can be compensated by other signals. This helps explain the relatively mild susceptibility to viral disease observed in STAT3- and IL-21R-deficient subjects.
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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.