ArticleThe Journal of clinical investigation2020
E4BP4-mediated inhibition of T follicular helper cell differentiation is compromised in autoimmune diseases.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 54 citations in OpenAlex.
- E4BP4 interacts with PERK to form a feedback loop mediating cold-induced female reproductive disorders.Cell stress & chaperones · 2026Article
- Transcription factor, E4BP4, inhibits autophagy and apoptosis in multiple myeloma and promotes the HDAC3-mediated suppression of the Beclin1 promoter to reduce dexamethasone sensitivity.Journal of translational medicine · 2026Article
- The impactful role of the HDACs in the regulation of gene expression and as targets for disease therapy.Science advances · 2026Review
- Lactate bridges mesangial cells to the differentiation of follicular helper T cells in lupus nephritis.Nature communications · 2025Article
- T follicular helper cells in primary immune regulatory disorders.The Journal of allergy and clinical immunology · 2025Review
- SETD3 regulates Bcl-6 expression and Tfh differentiation in SLE CD4Clinical epigenetics · 2025Article
- Polyfunctional T follicular helper cells drive checkpoint-inhibitor diabetes and are targeted by JAK inhibitor therapy.JCI insight · 2025Article
- High disease activity correlate with decreased serum calcium in systemic lupus erythematosus.Scientific reports · 2025Article
- Single-cell analyses of intestinal epithelium reveal the dysregulation of gut immune microenvironment in systemic lupus erythematosus.Journal of translational medicine · 2025Article
- Engineered cell therapies for autoimmune diseases: evaluating CAR-T and CAR-M progress and prospects.Frontiers in immunology · 2025Review
- Help me help you: emerging concepts in T follicular helper cell differentiation, identity, and function.Current opinion in immunology · 2024Review
- Review
- NFIL3 contributes to cytotoxic T lymphocyte-mediated killing.Open biology · 2024Article
- Neddylation is a novel therapeutic target for lupus by regulating double negative T cell homeostasis.Signal transduction and targeted therapy · 2024Article
- The role of basic leucine zipper transcription factor E4BP4 in cancer: a review and update.Molecular biology reports · 2024Review
- A pan-cancer characterization of immune-related NFIL3 identifies potential predictive biomarker.Journal of Cancer · 2024Article
- The critical importance of epigenetics in autoimmune-related skin diseases.Frontiers of medicine · 2023Review
- Identification of immune-related genes in diagnosing atherosclerosis with rheumatoid arthritis through bioinformatics analysis and machine learning.Frontiers in immunology · 2023Article
- Single-cell sequencing shows cellular heterogeneity of cutaneous lesions in lupus erythematosus.Nature communications · 2022Article
- LncRNA IL21-AS1 interacts with hnRNPU protein to promote IL21 overexpression and aberrant differentiation of Tfh cells in systemic lupus erythematosus.Clinical and translational medicine · 2022Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T follicular helper (Tfh) cells are indispensable for the formation of germinal center (GC) reactions, whereas T follicular regulatory (Tfr) cells inhibit Tfh-mediated GC responses. Aberrant activation of Tfh cells contributes substantially to the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE). Nonetheless, the molecular mechanisms mitigating excessive Tfh cell differentiation are not fully understood. Herein we demonstrate that the adenovirus E4 promoter-binding protein (E4BP4) mediates a feedback loop and acts as a transcriptional brake to inhibit Tfh cell differentiation. Furthermore, we show that such an immunological mechanism is compromised in patients with SLE. Establishing mice with either conditional knockout (cKO) or knockin (cKI) of the E4bp4 gene in T cells reveals that E4BP4 strongly inhibits Tfh cell differentiation. Mechanistically, E4BP4 regulates Bcl6 transcription by recruiting the repressive epigenetic modifiers HDAC1 and EZH2. E4BP4 phosphorylation site mutants have limited capability with regard to inhibiting Tfh cell differentiation. In SLE, we detected impaired phosphorylation of E4BP4, finding that this compromised transcription factor is positively correlated with disease activity. These findings unveiled molecular mechanisms by which E4BP4 restrains Tfh cell differentiation, whose compromised function is associated with uncontrolled autoimmune reactions in SLE.
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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.