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

Kahraman T., Gucluler G., ŞİMŞEK I., Yagci F. C., Yildirim M., ÖZEN C., ...More

JOURNAL OF EXTRACELLULAR VESICLES, vol.6, 2017 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 6
  • Publication Date: 2017
  • Doi Number: 10.1080/20013078.2017.1284449
  • Journal Name: JOURNAL OF EXTRACELLULAR VESICLES
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Keywords: Extracellular vesicles, Behcet's disease, autoimmune, immune activation, LL37, cytokine, SYSTEMIC-LUPUS-ERYTHEMATOSUS, APOLIPOPROTEIN-A-I, ENDOTHELIAL MICROPARTICLES, RHEUMATOID-ARTHRITIS, PLATELET MICROPARTICLES, PEPTIDE LL-37, ANTIMICROBIAL PEPTIDE, MULTIPLE-SCLEROSIS, DENDRITIC CELLS, RESPONSES
  • Middle East Technical University Affiliated: Yes

Abstract

Behcet'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 IL1 beta, IFN alpha, 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.