期刊
CLINICAL IMMUNOLOGY
卷 176, 期 -, 页码 12-22出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2016.12.005
关键词
Systemic lupus erythematosus; Estrogen; Innate immunity; microRNA (miR); Toll-like receptor (TLR)8; Extracellular vesicles
类别
资金
- NIH [R00-ES019918]
- National Center for Advancing Translational Science [UL1TR001070]
- Lupus Research Alliance
Recent studies implicate innate immunity to systemic lupus erythematosus (SLE) pathogenesis. Toll-like receptor (TLR)8 is estrogen-regulated and binds viral ssRNA to stimulate innate immune responses, but recent work indicates that microRNA (miR)-21 within extracellular vesicles (EVs) can also trigger this receptor. Our objective was to examine TLR8 expression/activation to better understand sex-biased responses involving TLR8 in SLE. Our data identify an estrogen response element that promotes STAT1 expression and demonstrate STAT1-dependent transcriptional activation of TLR8 with estrogen stimulation. In lieu of viral ssRNA activation, we explored EV-encapsulated miR-21 as an endogenous ligand and observed induction of both TLR8 and cytokine expression in vitro. Moreover, extracellular miR detection was found predominantly within EVs. Thus, just as a cytokine or chemokine, EV-encapsulated miR-21 can act as an inflammatory signaling molecule, or miRokine, by virtue of being an endogenous ligand of TLR8. Collectively, our data elucidates a novel innate inflammatory pathway in SLE. (C) 2017 The Authors. Published by Elsevier Inc.
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