Circulating LL37 targets plasma extracellular vesicles to immune cells and intensifies Behçet's disease severity
Author(s)
Date
2017-02Source Title
Journal of Extracellular Vesicles
Print ISSN
2001-3078
Publisher
Taylor and Francis
Volume
6
Issue
1
Pages
1284449-1 - 1284449-13
Language
English
Type
ArticleItem Usage Stats
284
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views
204
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Abstract
Behçet's disease (BD) activity is characterised by sustained, over-exuberant immune activation, yet the underlying mechanisms leading to active BD state are poorly defined. Herein, we show that the human cathelicidin derived antimicrobial peptide LL37 associates with and directs plasma extracellular vesicles (EV) to immune cells, thereby leading to enhanced immune activation aggravating BD pathology. Notably, disease activity was correlated with elevated levels of circulating LL37 and EV plasma concentration. Stimulation of healthy PBMC with active BD patient EVs induced heightened IL1β, IFNα, IL6 and IP10 secretion compared to healthy and inactive BD EVs. Remarkably, when mixed with LL37, healthy plasma-EVs triggered a robust immune activation replicating the pathology inducing properties of BD EVs. The findings of this study could be of clinical interest in the management of BD, implicating LL37/EV association as one of the major contributors of BD pathogenesis.
Keywords
AutoimmuneBehçet's disease
Cytokine
Extracellular vesicles
Immune activation
LL37
Alpha interferon
Biological marker
Cathelicidin
Cathelicidin antimicrobial peptide LL 37
Gamma interferon inducible protein 10
Glucose regulated protein 94
Interleukin 10
Interleukin 1beta
Interleukin 6
Protein Alix
Unclassified drug
Allogeneic extracellular vesicle
Article
Autologous extracellular vesicle
Behcet disease
Cell stimulation
Comparative study
Complex formation
Controlled study
Cytokine production
Cytokine release
Disease activity
Disease association
Disease severity
Exosome
Human
Human cell
Immune activation
Immune response
Immunocompetent cell
Incubation time
Internalization
Pathogenesis
Peripheral blood mononuclear cell
Plasma extracellular vesicle
Plasmacytoid dendritic cell
Permalink
http://hdl.handle.net/11693/37177Published Version (Please cite this version)
https://doi.org/10.1080/20013078.2017.1284449Collections
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