ArticleThe Journal of experimental medicine2022
Trapping of CDC42 C-terminal variants in the Golgi drives pyrin inflammasome hyperactivation.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Decoding variants of uncertain significance in systemic autoinflammatory diseases.Nature reviews. Rheumatology · 2026Review
- Immune-related actinopathies at the cross-road of immunodeficiency, autoimmunity and autoinflammation.Nature reviews. Immunology · 2026Review
- Familial Mediterranean Fever: A Comprehensive Review of Pathogenesis, Genetics, and Epigenetic Regulation.Balkan medical journal · 2026Review
- Recent variant discoveries and emerging genetic mechanisms in autoinflammatory diseases.Frontiers in immunology · 2026Review
- A novel compound heterozygous NBAS variant with HLH and multisystem involvement: expanding the clinical spectrum and literature review.Frontiers in immunology · 2026Review
- Inflammasome components as new therapeutic targets in inflammatory disease.Nature reviews. Immunology · 2025Review
- Autoinflammatory patients with Golgi-trapped CDC42 exhibit intracellular trafficking defects leading to STING hyperactivation and ER stress.Nature communications · 2024Article
- RAC2 gain-of-function variants causing inborn error of immunity drive NLRP3 inflammasome activation.The Journal of experimental medicine · 2024Article
- Human induced pluripotent stem cells (NIHTVBi029-A and NIHTVBi030-A) generated from two patients with a heterozygous mutation in the CDC42 gene.Stem cell research · 2024Article
- CircCDC42-encoded CDC42-165aa regulates macrophage pyroptosis in Klebsiella pneumoniae infection through Pyrin inflammasome activation.Nature communications · 2024Article
- Interrupting an IFN-γ-dependent feedback loop in the syndrome of pyogenic arthritis with pyoderma gangrenosum and acne.Annals of the rheumatic diseases · 2024Article
- Genetic Rare Variants Affecting Multiple Pathways in Japanese Patients with Palindromic Rheumatism.The Kobe journal of medical sciences · 2024Article
- Pyrin variant E148Q potentiates inflammasome activation and the effect of pathogenic mutations in cis.Rheumatology (Oxford, England) · 2024Article
- Cellular models in autoinflammatory disease research.Clinical & translational immunology · 2024Review
- Biological and clinical roles of IL-18 in inflammatory diseases.Nature reviews. Rheumatology · 2024Review
- The Multifaceted Immunology of Cytokine Storm Syndrome.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Biologics and JAK inhibitors for the treatment of monogenic systemic autoinflammatory diseases in children.The Journal of allergy and clinical immunology · 2023Review
- Lipidation of small GTPase Cdc42 as regulator of its physiological and pathophysiological functions.Frontiers in physiology · 2022Review
- Immune-mediated inflammatory diseases with chronic excess of serum interleukin-18.Frontiers in immunology · 2022Review
- Induced Pluripotent Stem Cell-Derived Monocytes/Macrophages in Autoinflammatory Diseases.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
23 authors at 5 institutions in 1 country.
Funding
Abstract
Mutations in the C-terminal region of the CDC42 gene cause severe neonatal-onset autoinflammation. Effectiveness of IL-1β-blocking therapy indicates that the pathology involves abnormal inflammasome activation; however, the mechanism underlying autoinflammation remains to be elucidated. Using induced-pluripotent stem cells established from patients carrying CDC42R186C, we found that patient-derived cells secreted larger amounts of IL-1β in response to pyrin-activating stimuli. Aberrant palmitoylation and localization of CDC42R186C protein to the Golgi apparatus promoted pyrin inflammasome assembly downstream of pyrin dephosphorylation. Aberrant subcellular localization was the common pathological feature shared by CDC42 C-terminal variants with inflammatory phenotypes, including CDC42*192C*24 that also localizes to the Golgi apparatus. Furthermore, the level of pyrin inflammasome overactivation paralleled that of mutant protein accumulation in the Golgi apparatus, but not that of the mutant GTPase activity. These results reveal an unexpected association between CDC42 subcellular localization and pyrin inflammasome activation that could pave the way for elucidating the mechanism of pyrin inflammasome formation.
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Registered trials
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