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Circulating exosomes from patients with systemic lupus erythematosus induce a proinflammatory immune response

Cited 55 time in Web of Science Cited 58 time in Scopus
Authors
Lee, Joo Youn; Park, Jin Kyun; Lee, Eun Young; Lee, Eun Bong; Song, Yeong Wook
Issue Date
2016-11-16
Publisher
BioMed Central
Citation
Arthritis Research & Therapy, 18(1):264
Keywords
Systemic lupus erythematosusExosomeCytokineInflammationToll-like receptor
Abstract
Background
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).

Methods
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.

Results
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).

Conclusions
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.
Language
English
URI
https://hdl.handle.net/10371/109904
DOI
https://doi.org/10.1186/s13075-016-1159-y
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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