ArticleCell communication and signaling : CCS2025
Extracellular vimentin is a damage-associated molecular pattern protein serving as an agonist of TLR4 in human neutrophils.
Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Crosstalk between vimentin and keratins in viral infection: Implications across the viral life cycle.Virulence · 2026Review
- Breaking the glial loop: astrocytic PAD2 and citrullinated vimentin drive microglial dysfunction in Alzheimer's disease.Molecular neurodegeneration · 2026Article
- Cross-presentation of citrullinated antigens drives cytotoxic CD8bioRxiv : the preprint server for biology · 2026Article
- Characterization of a distinct form of vimentin in the neurodegenerative brain.Acta neuropathologica communications · 2026Article
- DAMP signaling networks: from receptors to diverse pathophysiological functions.Journal of advanced research · 2026Review
- Tissue Reaction to Monofilament Grafts of Different Weights Used for Abdominal Wall Reinforcement.Biomedicines · 2026Article
- Modulating Vimentin: A Systems-Level Therapeutic Strategy for Sepsis and Complex Diseases.Life (Basel, Switzerland) · 2026Article
- Modified Dachengqi Decoction ameliorates sepsis-induced lung injury via the gut microbiota-bile acid axis.Frontiers in cellular and infection microbiology · 2026Article
- Neutrophil extracellular traps in antifungal immunity: mechanisms, dual roles, regulatory networks, and clinical perspectives.Frontiers in cellular and infection microbiology · 2026Review
- Cadmium exposure triggers vimentin phosphorylation via SIRT6-regulated AKT/PI3K signaling pathway in COPD.European journal of cell biology · 2025Article
- Annexin A2 Contributes to Release of Extracellular Vimentin in Response to Inflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
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13 authors.
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Abstract
backgroundVimentin is a type III intermediate filament protein that plays an important role in cytoskeletal mechanics. It is now known that vimentin also has distinct functions outside the cell. Recent studies show the controlled release of vimentin into the extracellular environment, where it functions as a signaling molecule. Such observations are expanding our current knowledge of vimentin as a structural cellular component towards additional roles as an active participant in cell signaling.
methodsOur study investigates the immunological roles of extracellular vimentin (eVim) and its citrullinated form (CitVim) as a damage-associated molecular pattern (DAMP) engaging the Toll-like receptor 4 (TLR4) of human neutrophils. We used in vitro assays to study neutrophil migration through endothelial cell monolayers and activation markers such as NADPH oxidase subunit 2 (NOX2/gp91phox). The comparison of eVim with CitVim and its effect on human neutrophils was extended to the induction of extracellular traps (NETs) and phagocytosis of pathogens.
resultsBoth eVim and CitVim interact with and trigger TLR4, leading to increased neutrophil migration and adhesion. CitVim stimulated the enhanced migratory ability of neutrophils, activation of NF-κB, and induction of NET formation mainly mediated through reactive oxygen species (ROS)-dependent and TLR4-dependent pathways. In contrast, neutrophils exposed to non-citrullinated vimentin exhibited higher efficiency in favoring pathogen phagocytosis, such as Escherichia coli and Candida albicans, compared to CitVim.
conclusionsOur study identifies new functions of eVim in its native and modified forms as an extracellular matrix DAMP and highlights its importance in the modulation of immune system functions. The differential effects of eVim and CitVim on neutrophil functions highlight their potential as new molecular targets for therapeutic strategies aimed at regulation of neutrophil activity in different pathological conditions. This, in turn, opens new windows of therapeutic intervention in inflammatory and immunological diseases characterized by immune system dysfunction, in which eVim and CitVim play a key role.
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