Yayınlanmış 1 Ocak 2017 | Sürüm v1

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

  • 1. Bilkent Univ, Fac Sci, Dept Mol Biol & Genet, Ankara, Turkey
  • 2. Gulhane Mil Med Acad, Div Rheumatol, Ankara, Turkey
  • 3. Middle East Tech Univ, Dept Biotechnol, Ankara, Turkey
  • 4. Middle East Tech Univ, Dept Biol Sci, Ankara, Turkey
  • 5. Sabanci Univ, Nanotechnol Res & Applicat Ctr, Istanbul, Turkey
  • 6. Univ Zurich Hosp, Dept Rheumatol, Zurich, Switzerland

Açıklama

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.

Dosyalar

bib-addd2e25-7453-47ce-8fcc-1798679c8c40.txt

Dosyalar (309 Bytes)

Ad Boyut Hepisini indir
md5:d4059c6bc8f9044f6baa3206205263b5
309 Bytes Ön İzleme İndir