ArticleEMBO molecular medicine2020
Resolving mechanisms of immune-mediated disease in primary CD4 T cells.
Article in EMBO molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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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
30 citing papers in PubMed, 45 citations in OpenAlex.
- Comprehensive mapping of genetic variation at Epromoters reveals pleiotropic association with multiple disease traits.Nucleic acids research · 2025Article
- Eleven Grand Challenges for Inflammatory Bowel Disease Genetics and Genomics.Inflammatory bowel diseases · 2025Review
- Current progress and future perspective of super-enhancers: a viable and effective bridge between the transcriptional apparatus and disease.Frontiers in genetics · 2025Review
- Super-enhancers in immune system regulation: mechanisms, pathological reprogramming, and therapeutic opportunities.Frontiers in immunology · 2025Review
- A systematic strategy for identifying causal single nucleotide polymorphisms and their target genes on Juvenile arthritis risk haplotypes.BMC medical genomics · 2024Article
- Article
- Identification of functional enhancer variants associated with type I diabetes in CD4+ T cells.Frontiers in immunology · 2024Article
- Inflammatory bowel disease and risk of ophthalmic inflammation-related diseases: a two-sample Mendelian randomization study.International journal of ophthalmology · 2024Article
- Systematic characterization of regulatory variants of blood pressure genes.Cell genomics · 2023Article
- Cis-regulatory atlas of primary human CD4+ T cells.BMC genomics · 2023Article
- Epigenetics as a mediator of genetic risk in osteoarthritis: role during development, homeostasis, aging, and disease progression.American journal of physiology. Cell physiology · 2023Review
- Three-dimensional genome organization in immune cell fate and function.Nature reviews. Immunology · 2023Review
- Hacking hematopoiesis - emerging tools for examining variant effects.Disease models & mechanisms · 2023Article
- Translating non-coding genetic associations into a better understanding of immune-mediated disease.Disease models & mechanisms · 2023Review
- The Evolution of Single-Cell RNA Sequencing Technology and Application: Progress and Perspectives.International journal of molecular sciences · 2023Review
- 3D genome organization and epigenetic regulation in autoimmune diseases.Frontiers in immunology · 2023Review
- Identification of the shared genetic architecture underlying seven autoimmune diseases with GWAS summary statistics.Frontiers in immunology · 2023Article
- "Stripe" transcription factors provide accessibility to co-binding partners in mammalian genomes.Molecular cell · 2022Article
- miR-374a-5p regulates inflammatory genes and monocyte function in patients with inflammatory bowel disease.The Journal of experimental medicine · 2022Article
- Functional interrogation of autoimmune disease genetics using CRISPR/Cas9 technologies and massively parallel reporter assays.Seminars in immunopathology · 2022Review
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 3 institutions in 2 countries.
Funding
Abstract
Deriving mechanisms of immune-mediated disease from GWAS data remains a formidable challenge, with attempts to identify causal variants being frequently hampered by strong linkage disequilibrium. To determine whether causal variants could be identified from their functional effects, we adapted a massively parallel reporter assay for use in primary CD4 T cells, the cell type whose regulatory DNA is most enriched for immune-mediated disease SNPs. This enabled the effects of candidate SNPs to be examined in a relevant cellular context and generated testable hypotheses into disease mechanisms. To illustrate the power of this approach, we investigated a locus that has been linked to six immune-mediated diseases but cannot be fine-mapped. By studying the lead expression-modulating SNP, we uncovered an NF-κB-driven regulatory circuit which constrains T-cell activation through the dynamic formation of a super-enhancer that upregulates TNFAIP3 (A20), a key NF-κB inhibitor. In activated T cells, this feedback circuit is disrupted-and super-enhancer formation prevented-by the risk variant at the lead SNP, leading to unrestrained T-cell activation via a molecular mechanism that appears to broadly predispose to human autoimmunity.
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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.