ArticleImmunity2012
Interleukin-4 production by follicular helper T cells requires the conserved Il4 enhancer hypersensitivity site V.
Article in Immunity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 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.
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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
88 citing papers in PubMed, 155 citations in OpenAlex.
- Effect of theNutrients · 2020Trial
- Regulation of follicular helper T cell subset differentiation in health and disease.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Interleukin-4-producing type 2 innate lymphoid cells in the lymph node promote proallergic Tfh13 cell differentiation.Immunity · 2026Article
- Mixed Signals: T Cells as Architects of IgE Immunity.Immunological reviews · 2026Review
- Potential Cosmetic Applications of the Combined Extract of Panax ginseng, Ganoderma lucidum, Cordyceps militaris, and Several Asian Plants.Journal of cosmetic dermatology · 2025Article
- Mechanisms of vaccine protection in chickens against challenge with virulent Mycoplasma synoviae.Veterinary research · 2025Article
- Thymic stromal lymphopoietin improves protective immunity of the SARS-CoV-2 subunit vaccine by inducing dendritic cell-dependent germinal center response.Journal of virology · 2025Article
- Impact of Lithium on the Immune System: An Investigation of T-Cell Subpopulations and Cytokine Responses in Rats.Biological trace element research · 2025Article
- Follicular helper T cells (Tfh): heterogeneity in spatial distribution and phenotypic characteristics.Frontiers in immunology · 2025Review
- Remodeling of Il4-Il13-Il5 locus underlies selective gene expression.Nature immunology · 2024Article
- T follicular regulatory cells in food allergy promote IgE via IL-4.JCI insight · 2024Article
- Control of germinal center B cell survival and IgE production by an adaptor molecule containing PH and SH2 domains, Aps/Sh2b2.Scientific reports · 2024Article
- Predicting gene expression state and prioritizing putative enhancers using 5hmC signal.Genome biology · 2024Article
- Regulation of T helper cell differentiation by the interplay between histone modification and chromatin interaction.Immunity · 2024Article
- Anti-PD-1 therapy triggers Tfh cell-dependent IL-4 release to boost CD8 T cell responses in tumor-draining lymph nodes.The Journal of experimental medicine · 2024Article
- Efficacy of Topical Application of a Skin Moisturizer Containing Pseudo-Ceramide and a Eucalyptus Leaf Extract on Atopic Dermatitis: A Review.Journal of clinical medicine · 2024Review
- Cytokines in Follicular Helper T Cell Biology in Physiologic and Pathologic Conditions.Immune network · 2024Review
- Targeting interleukin 4 and interleukin 13: a novel therapeutic approach in bullous pemphigoid.Annals of medicine · 2023Review
- Diet-mediated constitutive induction of novel IL-4+ ILC2 cells maintains intestinal homeostasis in mice.The Journal of experimental medicine · 2023Article
- T helper 2 cells in asthma.The Journal of experimental medicine · 2023Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Follicular helper T cells (Tfh cells) are the major producers of interleukin-4 (IL-4) in secondary lymphoid organs where humoral immune responses develop. Il4 regulation in Tfh cells appears distinct from the classical T helper 2 (Th2) cell pathway, but the underlying molecular mechanisms remain largely unknown. We found that hypersensitivity site V (HS V; also known as CNS2), a 3' enhancer in the Il4 locus, is essential for IL-4 production by Tfh cells. Mice lacking HS V display marked defects in type 2 humoral immune responses, as evidenced by abrogated IgE and sharply reduced IgG1 production in vivo. In contrast, effector Th2 cells that are involved in tissue responses were far less dependent on HS V. HS V facilitated removal of repressive chromatin marks during Th2 and Tfh cell differentiation and increased accessibility of the Il4 promoter. Thus, Tfh and Th2 cells utilize distinct but overlapping molecular mechanisms to regulate Il4, a finding with important implications for understanding the molecular basis of allergic diseases.
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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.