ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
NLRC3 expression in macrophage impairs glycolysis and host immune defense by modulating the NF-κB-NFAT5 complex during septic immunosuppression.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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44 citing papers in PubMed, 60 citations in OpenAlex.
- Targeting the NR1D1-IGF2BP2-V-ATPase Axis With Hybrid Nanovesicles Restores Macrophage Rhythms to Reverse Sepsis-Induced Immunosuppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Intracellular LRG1 recruits MARCH2 to ubiquitinate and degrade endothelial VE-cadherin in septic lung injury.Acta pharmacologica Sinica · 2026Article
- NLRC3 in septic immunosuppression: Variation in expression and mechanisms of mediating immune cell dysfunction (Review).Experimental and therapeutic medicine · 2026Review
- ERK/Smurf1 regulates non-canonical pyroptosis by prompting Caspase-11 ubiquitination.Cell death and differentiation · 2026Article
- Metabolic reprogramming regulates macrophage polarization to impact ovarian cancer progression.Discover oncology · 2026Review
- Macrophage metabolism reprogramming in sepsis: Pathogenesis and therapeutic implications (Review).International journal of molecular medicine · 2026Review
- Long noncoding RNA Nron and its functional motif modulate macrophage-mediated inflammatory response.Journal of advanced research · 2026Article
- ACOD1 expression in patients with sepsis: an exploratory study of associations with disease severity and immune signatures.BMC infectious diseases · 2026Article
- PRC1 promotes immunosuppressive macrophages in sepsis via β-catenin/STAT3 signaling.Cellular and molecular life sciences : CMLS · 2026Article
- Type II Alveolar Epithelial Cells Promote Sepsis-Induced Immunosuppression in Alveolar Macrophages via Exosomal lncRNA Rmrp Release.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Gut-derived small extracellular vesicles support trained innate immune tolerance in murine microglial cells.Frontiers in immunology · 2026Article
- Immunometabolic Reprogramming in Experimental Sepsis: A Driver of Multiple Organ Dysfunction Syndrome.Journal of inflammation research · 2026Review
- Interaction networks of macrophage glycolysis and inflammation in sepsis: mechanisms and therapeutic potential.Frontiers in immunology · 2026Review
- Delphinidin-3-O-glucoside attenuates neonatal hypoxic-ischemic encephalopathy in a neonatal mouse model by reprogramming microglial polarization.Frontiers in pharmacology · 2026Article
- Agonist signaling drives neutrophil subpopulations to promote/inhibit colorectal cancer liver metastasis.Nature communications · 2025Article
- Lipopolysaccharide-induced histone lactylation mediates m6A RNA modification causing mitochondrial dysfunction and pulmonary fibroblasts activation to exacerbate sepsis-associated pulmonary fibrosis.Respiratory research · 2025Article
- Peroxiredoxin 4 as a switch regulating PTEN/AKT axis in alveolar macrophages activation.Signal transduction and targeted therapy · 2025Article
- Article
- Role of NLRC3 in modulating inflammatory responses in neonates.BMC pediatrics · 2025Article
- Curcumin Modulates PTPRZ1 Activity and RNA m6A Modifications in Neuroinflammation-Associated Microglial Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
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Abstract
Impairment of innate immune cell function and metabolism underlies immunosuppression in sepsis; however, a promising therapy to orchestrate this impairment is currently lacking. In this study, high levels of NOD-like receptor family CARD domain containing-3 (NLRC3) correlated with the glycolytic defects of monocytes/macrophages from septic patients and mice that developed immunosuppression. Myeloid-specific NLRC3 deletion improved macrophage glycolysis and sepsis-induced immunosuppression. Mechanistically, NLRC3 inhibits nuclear factor (NF)-κB p65 binding to nuclear factor of activated T cells 5 (NFAT5), which further controls the expression of glycolytic genes and proinflammatory cytokines of immunosuppressive macrophages. This is achieved by decreasing NF-κB activation-co-induced by TNF-receptor-associated factor 6 (TRAF6) or mammalian target of rapamycin (mTOR)-and decreasing transcriptional co-activator p300 activity by inducing NLRC3 sequestration of mTOR and p300. Genetic inhibition of NLRC3 disrupted the NLRC3-mTOR-p300 complex and enhanced NF-κB binding to the NFAT5 promoter in concert with p300. Furthermore, intrapulmonary delivery of recombinant adeno-associated virus harboring a macrophage-specific NLRC3 deletion vector significantly improved the defense of septic mice that developed immunosuppression upon secondary intratracheal bacterial challenge. Collectively, these findings indicate that NLRC3 mediates critical aspects of innate immunity that contribute to an immunocompromised state during sepsis and identify potential therapeutic targets.
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