title: Circulating exosomes from patients with systemic lupus erythematosus induce an proinflammatory immune response.
abstract: Exosomes are involved in intercellular communication. The aim of this study was to investigate whether circulating exosomes effectively contribute to the inflammatory response in systemic lupus erythematosus (SLE).
  
  
  
  Exosomes were purified from SLE patients and healthy controls (HCs). Healthy peripheral blood mononuclear cells (PBMCs) were stimulated with exosomes isolated from SLE patients and HCs in the presence or absence of Toll-like receptor (TLR) inhibitors. Production of interferon (IFN)-α, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were measured. Correlation between exosome levels and SLE disease activity was examined.
  
  
  
  The serum exosomes levels were significantly higher in SLE patients than in HCs. SLE exosomes induced a higher production of IFN-α, TNF-α, IL-1β, and IL-6 compared to healthy exosomes. SLE serum that was depleted of exosomes and SLE exosomes that were mechanically disrupted failed to induce any significant cytokine production. Exosome-mediated production of TNF-α, IL-1β, and IL-6 was decreased by the TLR4 antagonist, whereas that of IFN-α was suppressed by the TLR1/2, TLR7, and TLR9 antagonists. Exosome levels correlated with disease activity in SLE patients (rho = 0.846, p = 0.008).
  
  
  
  The circulating exosomes are immunologically active and their levels correlate with disease activity in SLE patients. The circulating exosomes might serve as novel biomarkers of SLE disease activity.
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, BK 21 plus Graduate School of Convergence Science and Technology, and College of Medicine, Medical Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Joo Youn
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, BK 21 plus Graduate School of Convergence Science and Technology, and College of Medicine, Medical Research Institute, Seoul National University, Seoul, Korea.|Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Daehak-ro, Jongno-gu, Seoul, 03082, Korea.
authors.forename: Jin Kyun
authors.initials: JK
authors.lastname: Park
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Daehak-ro, Jongno-gu, Seoul, 03082, Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Lee
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Daehak-ro, Jongno-gu, Seoul, 03082, Korea.
authors.forename: Eun Bong
authors.initials: EB
authors.lastname: Lee
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, BK 21 plus Graduate School of Convergence Science and Technology, and College of Medicine, Medical Research Institute, Seoul National University, Seoul, Korea. ysong@snu.ac.kr.|Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Daehak-ro, Jongno-gu, Seoul, 03082, Korea. ysong@snu.ac.kr.
authors.forename: Yeong Wook
authors.initials: YW
authors.lastname: Song
mesh_terms: D000328:Adult; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D055354:Exosomes / Q000276:immunology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged
chemical_list: D016207:Cytokines
keywords: Cytokine; Exosome; Inflammation; Systemic lupus erythematosus; Toll-like receptor