ArticleJCI insight2024
Loss of PADI2 and PADI4 ameliorates sepsis-induced acute lung injury by suppressing NLRP3+ macrophages.
Article in JCI insight, 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.
- Mechanisms and therapeutic strategies of pyroptosis in sepsis‑induced acute lung injury (Review).International journal of molecular medicine · 2026Review
- A biomimetic microphysiological system predicts the impact of sepsis therapeutics on neutrophil-endothelial dynamics.Lab on a chip · 2026Article
- Comprehensive bioinformatics and experimental analysis of PPOX reveals its carcinogenic effect in clear cell renal cell carcinoma.Translational andrology and urology · 2026Article
- HMGB1-mediated formation of IL-33-abundant NETs drives lung-to-kidney injury in severe pneumonia-associated acute kidney injury.JCI insight · 2026Article
- CMPK2 restrictsbioRxiv : the preprint server for biology · 2026Article
- Advances in the mechanisms of the NLRP3 inflammasome in sepsis‑induced cardiomyopathy and targeted therapeutic studies (Review).Molecular medicine reports · 2026Review
- FGF 13 functions as a regulator of the ERK/aerobic glycolysis axis in the inflammatory state during septic lung injury.Nature communications · 2026Article
- Role of peptidylarginine deiminase 2 in a murine model of traumatic brain injury.The journal of trauma and acute care surgery · 2026Article
- Mapping benefit, risk, and opportunity in PAD4 inhibition.Frontiers in immunology · 2026Review
- Neutrophil extracellular traps associated with severity and prognosis of community-acquired pneumonia.Clinical and experimental medicine · 2025Article
- Sex-dependent effects of peptidylarginine deiminases on neutrophil function and long-term outcomes after spinal cord injury.Experimental neurology · 2025Article
- CitH3, a Druggable Biomarker for Human Diseases Associated with Acute NETosis and Chronic Immune Dysfunction.Pharmaceutics · 2025Review
- Protective effects ofFrontiers in nutrition · 2025Article
- Macrophage pyroptosis and its crucial role in ALI/ARDS.Frontiers in immunology · 2025Review
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Authors and funding
14 authors.
Funding
Abstract
Sepsis-induced acute lung injury (ALI) is prevalent in patients with sepsis and has a high mortality rate. Peptidyl arginine deiminase 2 (PADI2) and PADI4 play crucial roles in mediating the host's immune response in sepsis, but their specific functions remain unclear. Our study shows that Padi2-/- Padi4-/- double KO (DKO) improved survival, reduced lung injury, and decreased bacterial load in Pseudomonas aeruginosa (PA) pneumonia-induced sepsis mice. Using single-cell RNA-Seq (scRNA-Seq), we found that the deletion of Padi2 and Padi4 reduced the Nlrp3+ proinflammatory macrophages and fostered Chil3+ myeloid cell differentiation into antiinflammatory macrophages. Additionally, we observed the regulatory role of the NLRP3/Ym1 axis upon DKO, confirmed by Chil3 knockdown and Nlrp3-KO experiments. Thus, eliminating Padi2 and Padi4 enhanced the polarization of Ym1+ M2 macrophages by suppressing NLRP3, aiding in inflammation resolution and lung tissue repair. This study unveils the PADIs/NLRP3/Ym1 pathway as a potential target in treatment of sepsis-induced ALI.
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