ArticleThe Journal of experimental medicine2024
Large-scale mutational analysis identifies UNC93B1 variants that drive TLR-mediated autoimmunity in mice and humans.
Article in The Journal of experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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Who cites it
26 citing papers in PubMed.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- TLR7 in systemic lupus erythematosus: genetics and emerging therapies.Nature reviews. Rheumatology · 2026Review
- Identification of a novel TLR7 gain-of-function variant that underlies systemic lupus erythematosus.Journal of human immunity · 2026Article
- Novel TLR7 gain-of-function variant and review of the associated disease spectrum.Journal of human immunity · 2026Article
- TLR7 and TLR9 have overlapping but distinct roles in systemic lupus erythematosus and Sjögren's disease.Frontiers in immunology · 2026Review
- NOTCH3 attenuates cytotoxicity via RBPJ-dependent PVR upregulation to influence immunotherapy outcomes in colorectal cancer.Frontiers in immunology · 2026Article
- Juvenile-onset Systemic Lupus Erythematosus: Recent Advances in Pathogenesis and Treatment.Current rheumatology reports · 2025Review
- Interferons in health and disease.Cell · 2025Review
- Spondyloenchondrodysplasia: An enigmatic immuno-osseus type I interferonopathy.Journal of human immunity · 2025Article
- Insights from the 2024 pediatric rheumatology basic/translational years in review.Pediatric rheumatology online journal · 2025Review
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- Altered X-chromosome inactivation of the TLR7/8 locus and heterogeneity of pDCs in systemic sclerosis.The Journal of experimental medicine · 2025Article
- Genetic and epigenetic factors shape phenotypes and outcomes in systemic lupus erythematosus - focus on juvenile-onset systemic lupus erythematosus.Current opinion in rheumatology · 2025Review
- RNA sensing at the crossroads of autoimmunity and autoinflammation.RNA (New York, N.Y.) · 2025Review
- RNA sensing at the crossroads of autoimmunity and autoinflammation.RNA (New York, N.Y.) · 2025Review
- The emergence of SLE-causing UNC93B1 variants in 2024.Nature reviews. Rheumatology · 2025Article
- How (Ultra-)Rare Gene Variants Improve Our Understanding of More Common Autoimmune and Inflammatory Diseases.ACR open rheumatology · 2025Review
- Targeting toll-like receptors: unveiling potential therapeutic strategies for deep vein thrombosis.Frontiers in immunology · 2025Review
- Case Report: NovelFrontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
25 authors.
Funding
Abstract
Nucleic acid-sensing Toll-like receptors (TLR) 3, 7/8, and 9 are key innate immune sensors whose activities must be tightly regulated to prevent systemic autoimmune or autoinflammatory disease or virus-associated immunopathology. Here, we report a systematic scanning-alanine mutagenesis screen of all cytosolic and luminal residues of the TLR chaperone protein UNC93B1, which identified both negative and positive regulatory regions affecting TLR3, TLR7, and TLR9 responses. We subsequently identified two families harboring heterozygous coding mutations in UNC93B1, UNC93B1+/T93I and UNC93B1+/R336C, both in key negative regulatory regions identified in our screen. These patients presented with cutaneous tumid lupus and juvenile idiopathic arthritis plus neuroinflammatory disease, respectively. Disruption of UNC93B1-mediated regulation by these mutations led to enhanced TLR7/8 responses, and both variants resulted in systemic autoimmune or inflammatory disease when introduced into mice via genome editing. Altogether, our results implicate the UNC93B1-TLR7/8 axis in human monogenic autoimmune diseases and provide a functional resource to assess the impact of yet-to-be-reported UNC93B1 mutations.
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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.