ArticleCell reports. Medicine2024
Truncating NFKB1 variants cause combined NLRP3 inflammasome activation and type I interferon signaling and predispose to necrotizing fasciitis.
Article in Cell reports. Medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- Genotype-phenotype analysis in 333 individuals with heterozygous variants in NFKB1.Journal of human immunity · 2027Article
- ELF3/miR-9-5p/NFKB1 axis promotes the progression of osteoarthritis by triggering NLRP3-mediated cell pyroptosis.Immunologic research · 2026Article
- Heterozygous NFKB1 variant causes inflammatory dysregulation shaped by broader genetic context in common variable immunodeficiency.JCI insight · 2026Article
- Integrated multi-omics profiling identifies aging-related molecular signatures and convergent interferon signaling in systemic lupus erythematosus.Frontiers in immunology · 2026Article
- Clinical and immunological characterization ofFrontiers in immunology · 2026Article
- Host-response trajectories in necrotizing fasciitis: host-pathogen interactions, immune evasion, and immunoparalysis.Frontiers in cellular and infection microbiology · 2026Review
- Recent variant discoveries and emerging genetic mechanisms in autoinflammatory diseases.Frontiers in immunology · 2026Review
- Role of gut microbiota metabolites against vein graft restenosis: insights from network pharmacology, molecular docking and molecular dynamic simulation.BMC medical genomics · 2025Article
- BRD-K20733377 inhibits ferroptosis and alleviates intervertebral disc degeneration via the STAT3/NFKB1 axis: a multiapproach study.Stem cell research & therapy · 2025Article
- Anti-Inflammatory Effects of Spexin on Acetic Acid‑Induced Colitis in Rats via Modulating the NF-κB/NLRP3 Inflammasome Pathway.Journal of biochemical and molecular toxicology · 2025Article
- Common Variable Immunodeficiency Clinical Manifestations Are Shaped by Presence and Type of Heterozygous NFKB1 Variants.The journal of allergy and clinical immunology. In practice · 2025Article
- TPL2 kinase activity is required forFrontiers in immunology · 2025Article
- Lobetyolin Suppressed Osteoclastogenesis and Alleviated Bone Loss in Ovariectomy-Induced Osteoporosis via Hindering p50/p65 Nuclear Translocation and Downstream NFATc1/c-Fos Expression.Drug design, development and therapy · 2025Article
- A novel splice-site mutation in NFKB1 presenting as common variable immunodeficiency and postoperative hyperinflammation responsive to anti-IL-1 therapy.The journal of allergy and clinical immunology. In practice · 2024Article
Corrections and comments
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Authors and funding
32 authors at 10 institutions in 5 countries.
Funding
Abstract
In monogenic autoinflammatory diseases, mutations in genes regulating innate immune responses often lead to uncontrolled activation of inflammasome pathways or the type I interferon (IFN-I) response. We describe a mechanism of autoinflammation potentially predisposing patients to life-threatening necrotizing soft tissue inflammation. Six unrelated families are identified in which affected members present with necrotizing fasciitis or severe soft tissue inflammations. Exome sequencing reveals truncating monoallelic loss-of-function variants of nuclear factor κ light-chain enhancer of activated B cells (NFKB1) in affected patients. In patients' macrophages and in NFKB1-variant-bearing THP-1 cells, activation increases both interleukin (IL)-1β secretion and IFN-I signaling. Truncation of NF-κB1 impairs autophagy, accompanied by the accumulation of reactive oxygen species and reduced degradation of inflammasome receptor nucleotide-binding oligomerization domain, leucine-rich repeat-containing protein 3 (NLRP3), and Toll/IL-1 receptor domain-containing adaptor protein inducing IFN-β (TRIF), thus leading to combined excessive inflammasome and IFN-I activity. Many of the patients respond to anti-inflammatory treatment, and targeting IL-1β and/or IFN-I signaling could represent a therapeutic approach for these patients.
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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.