Circulating LL37 targets plasma extracellular vesicles to immune cells and intensifies Behçet's disease severity

Date
2017-02
Authors
Kahraman, T.
Gucluler, G.
Simsek, I.
Yagci, F. C.
Yildirim, M.
Ozen, C.
Dinc, A.
Gursel, M.
Ikromzoda, L.
Sutlu, T.
Advisor
Supervisor
Co-Advisor
Co-Supervisor
Instructor
Source Title
Journal of Extracellular Vesicles
Print ISSN
2001-3078
Electronic ISSN
Publisher
Taylor and Francis
Volume
6
Issue
1
Pages
1284449-1 - 1284449-13
Language
English
Type
Article
Journal Title
Journal ISSN
Volume Title
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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.

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Keywords
Autoimmune, Behçet'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
Citation
Published Version (Please cite this version)