ArticleThe Journal of experimental medicine2020
IL-21 is a broad negative regulator of IgE class switch recombination in mouse and human B cells.
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 108 citations in OpenAlex.
- Clinical features, genetics, treatment, and long-term outcomes of STAT3 hyper-IgE syndrome: Single-center cohort analysis.The Journal of allergy and clinical immunology · 2026Observational
- Allergic Sensitization to Inhalant Allergens in the Upper Respiratory Tract-the B Cell Side.Allergy · 2026Review
- Multiple roads to IgE memory: A pluralistic model of IgE immunity.Cell reports · 2026Review
- Mixed Signals: T Cells as Architects of IgE Immunity.Immunological reviews · 2026Review
- Article
- Pathophysiological and molecular insights into allergic conjunctivitis: an expanding analysis of immunological endotypes.Frontiers in allergy · 2026Review
- IL-21 expression during sublingual immunotherapy for allergic rhinitis.American journal of clinical and experimental immunology · 2026Article
- Unique chicken B cell development: species-specific mechanisms and contradictory requirements of B cell receptor for post-hatched B cell development.Frontiers in immunology · 2026Review
- Impact of kynurenine metabolites on B and T cells in multiple sclerosis and allergies.IBRO neuroscience reports · 2025Review
- Review
- Efficacy of omalizumab in the treatment of STAT3 loss-of-function mutations associated with autosomal dominant hyperimmunoglobulin E syndrome-a case report.Translational pediatrics · 2025Article
- STAT3 haploinsufficiency is associated with autosomal dominant hyper-IgE syndrome.Science advances · 2025Article
- Allergic Reactivity and Memory Occur Independently of Sequential Switching Through IgG1.Allergy · 2025Article
- Development of a peptide-based vaccine using a T cell epitope derived from SARS-CoV-2.iScience · 2025Article
- Lung-resident memory B cells maintain allergic IgE responses in the respiratory tract.Immunity · 2025Article
- Progressively differentiated TNature immunology · 2025Article
- IL-2 family cytokines IL-9 and IL-21 differentially regulate innate and adaptive type 2 immunity in asthma.The Journal of allergy and clinical immunology · 2024Article
- Pathophysiology of Congenital High Production of IgE and Its Consequences: A Narrative Review Uncovering a Neglected Setting of Disorders.Life (Basel, Switzerland) · 2024Review
- Prospective Variation of Cytokine Trends during COVID-19: A Progressive Approach from Disease Onset until Outcome.International journal of molecular sciences · 2024Article
- Whence and wherefore IgE?Immunological reviews · 2024Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
IgE antibodies may elicit potent allergic reactions, and their production is tightly controlled. The tendency to generate IgE has been thought to reflect the balance between type 1 and type 2 cytokines, with the latter promoting IgE. Here, we reevaluated this paradigm by a direct cellular analysis, demonstrating that IgE production was not limited to type 2 immune responses yet was generally constrained in vivo. IL-21 was a critical negative regulator of IgE responses, whereas IFN-γ, IL-6, and IL-10 were dispensable. Follicular helper T cells were the primary source of IL-21 that inhibited IgE responses by directly engaging the IL-21 receptor on B cells and triggering STAT3-dependent signaling. We reconciled previous discordant results between mouse and human B cells and revealed that the inhibition of IgE class switch recombination by IL-21 was attenuated by CD40 signaling, whereas IgG1 class switch recombination was potentiated by IL-21 in the context of limited IL-4. These findings establish key features of the extrinsic regulation of IgE production by cytokines.
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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.