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

Journal of Extracellular Vesicles

Ayhan Dinc¹  Tamer Kahraman¹  Ismail Simsek¹  Muzaffer Yildirim¹  Mayda Gursel¹  Gozde Gucluler¹  Fuat Cem Yagci¹  Lolai Ikromzoda¹  Can Ozen¹  Tolga Sutlu¹ 

关键词: Extracellular vesicles;    Behçet’s disease;    autoimmune;    immune activation;    LL37;    cytokine;   

DOI  :  10.1080/20013078.2017.1284449

来源: Co-Action Publishing

【 摘 要 】

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.

【 授权许可】

Unknown