ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Citrullination of NF-κB p65 by PAD2 as a Novel Therapeutic Target for Modulating Macrophage Polarization in Acute Lung Injury.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- NEMO (IKKγ) citrullination in microglia promotes neuroinflammation in the post-ischemic brain.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- IRAK-M Knockout Exacerbates Inflammation in Mice Infected withMicroorganisms · 2026Article
- Review
- Metal-based nanoparticles for reprogramming macrophage polarization: Advances in immunomodulatory nanotherapeutics.International journal of pharmaceutics: X · 2026Review
- Dopamine signaling governs macrophage-mediated acute lung injury through JAML/IL-10-coupled mitochondrial regulation.Journal of neuroinflammation · 2026Article
- Role of peptidylarginine deiminase 2 in a murine model of traumatic brain injury.The journal of trauma and acute care surgery · 2026Article
- Ventilator-Induced Lung Injury: Mechanotransduction and Potential Therapeutic Targets.MedComm · 2026Review
- Mapping benefit, risk, and opportunity in PAD4 inhibition.Frontiers in immunology · 2026Review
- PADI2 exacerbates Mycoplasma ovipneumoniae-induced lung injury in sheep by suppressing M2 macrophage polarization.Veterinary research · 2025Article
- Citrullination of NF-κB p65 by PAD2 as a Novel Therapeutic Target for Modulating Macrophage Polarization in Acute Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
12 authors.
Funding
Abstract
Mediating protein citrullination, peptidyl arginine deiminase 2 (PAD2) has recently been reported to influence macrophage phenotypes. However, the mechanisms of PAD2 on macrophage function in Pseudomonas aeruginosa (PA)-induced acute lung injury syndrome (ALI) remains unclear. Utilizing single-cell RNA sequencing and mass spectrometry-based proteomics, a new citrullination site at arginine 171 (R171) is discovered within nuclear factor- κB (NF-κB) p65 catalyzed by PAD2, which modulates PAD2-NF-κB p65-importin α3 pathway and its downstream M1/M2 macrophage polarization. Building on these findings, a cell-specific targeted therapeutic strategy using gold nanoparticles (AuNPs) conjugated with a novel PAD2 inhibitor, AFM41a, and an intercellular adhesion molecule-1 (ICAM-1) antibody is developed. This approach enables the selective delivery of the inhibitor to M1-polarized macrophages in the PA-infected alveolar niche. In vivo, this nanomedicine reduces excessive inflammation and promotes M1-to-M2 polarization to inhibit ALI. This study highlights the role of PAD2-mediated citrullination in macrophage polarization and introduces a promising nanoparticle-based therapy for PA-induced ALI.
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