ArticleScience immunology2021
DDX17 is an essential mediator of sterile NLRC4 inflammasome activation by retrotransposon RNAs.
Article in Science immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 50 citations in OpenAlex.
- Oral lamivudine in diabetic macular edema: A randomized, double-blind, placebo-controlled clinical trial.Med (New York, N.Y.) · 2025Trial
- DDX17 and viral infection.Virulence · 2026Review
- YBX1 regulates RNA polymerase III transcripts to prevent inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- RNA helicase DDX6 governs ASC speck formation in P-bodies and the transition to stress granules via phase separation during inflammasome activation.Cell discovery · 2026Article
- Systematic dysregulation of immune-related alternative polyadenylation in systemic lupus erythematosus contributes to patient stratification.Journal of translational autoimmunity · 2026Article
- The Role of Non-LTR Retrotransposons in Sterile Inflammation: Mechanisms and Therapeutic Potential.Biomedicines · 2026Review
- NAT10 Promotes Tubular Epithelial Cell Senescence in Cisplatin-Induced Acute Kidney Injury by Regulating DDX17.International journal of biological sciences · 2026Article
- Gasdermins in neurodegeneration: emerging mechanisms and therapeutic targets.Cell death & disease · 2025Review
- An animal model of NLRC4-associated autoinflammation and infantile enterocolitis reveals novel therapeutic strategies.Cellular & molecular immunology · 2025Article
- [Silencing DDX17 inhibits proliferation and migration of pulmonary arterial smooth muscle cellsNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.Cellular & molecular immunology · 2025Review
- Intron retention: a novel method for evaluating the response to ketamine in patients with treatment-resistant depression.Npj mental health research · 2025Article
- An atlas of single-cell eQTLs dissects autoimmune disease genes and identifies novel drug classes for treatment.Cell genomics · 2025Article
- PANoptosis in neurological disorders: mechanisms, implications, and therapeutic potential.Frontiers in immunology · 2025Review
- LRRK2-mediated NLRC4 phosphorylation differentially regulates IL-1β/IL-18 secretion.Frontiers in immunology · 2025Article
- The advances of DEAD-box RNA helicase 17 in chronic non-infectious diseases.Frontiers in cardiovascular medicine · 2025Review
- Activation of Inflammasomes and Relevant Modulators for the Treatment of Microglia-mediated Neuroinflammation in Ischemic Stroke.Molecular neurobiology · 2024Review
- Inflammasome activation aggravates choroidal neovascularization.Angiogenesis · 2024Article
- DAMP sensing and sterile inflammation: intracellular, intercellular and inter-organ pathways.Nature reviews. Immunology · 2024Review
- Identification and coregulation pattern analysis of long noncoding RNAs in the mouse brain after Angiostrongylus cantonensis infection.Parasites & vectors · 2024Article
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24 authors at 8 institutions in 3 countries.
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Abstract
Detection of microbial products by multiprotein complexes known as inflammasomes is pivotal to host defense against pathogens. Nucleotide-binding domain leucine-rich repeat (NLR) CARD domain containing 4 (NLRC4) forms an inflammasome in response to bacterial products; this requires their detection by NLR family apoptosis inhibitory proteins (NAIPs), with which NLRC4 physically associates. However, the mechanisms underlying sterile NLRC4 inflammasome activation, which is implicated in chronic noninfectious diseases, remain unknown. Here, we report that endogenous short interspersed nuclear element (SINE) RNAs, which promote atrophic macular degeneration (AMD) and systemic lupus erythematosus (SLE), induce NLRC4 inflammasome activation independent of NAIPs. We identify DDX17, a DExD/H box RNA helicase, as the sensor of SINE RNAs that licenses assembly of an inflammasome comprising NLRC4, NLR pyrin domain–containing protein 3, and apoptosis-associated speck-like protein–containing CARD and induces caspase-1 activation and cytokine release. Inhibiting DDX17-mediated NLRC4 inflammasome activation decreased interleukin-18 release in peripheral blood mononuclear cells of patients with SLE and prevented retinal degeneration in an animal model of AMD. Our findings uncover a previously unrecognized noncanonical NLRC4 inflammasome activated by endogenous retrotransposons and provide potential therapeutic targets for SINE RNA–driven diseases.
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