Exosomal delivery of NF-kappa B inhibitor delays LPS-induced preterm birth and modulates fetal immune cell profile in mouse models

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Accumulation of immune cells and activation of the pro-inflammatory transcription factor NF-kappa B in feto-maternal uterine tissues is a key feature of preterm birth (PTB) pathophysiology. Reduction of the fetal inflammatory response and NF-kappa B activation are key strategies to minimize infection-associated PTB. Therefore, we engineered extracellular vesicles (exosomes) to contain an NF-kappa B inhibitor, termed super-repressor (SR) I kappa B alpha. Treatment with SR exosomes (1 x 10(10 )per intraperitoneal injection) after lipopolysaccharide (LPS) challenge on gestation day 15 (E15) prolonged gestation by over 24 hours (PTB <= E18.5) and reduced maternal inflammation (n >= 4). Furthermore, using a transgenic model in which fetal tissues express the red fluorescent protein tdTomato while maternal tissues do not, we report that LPS-induced PTB in mice is associated with influx of fetal innate immune cells, not maternal, into feto-maternal uterine tissues. SR packaged in exosomes provides a stable and specific intervention for reducing the inflammatory response associated with PTB.
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Issue Date
2021-01
Language
English
Article Type
Article
Citation

SCIENCE ADVANCES, v.7, no.4, pp.eabd3865

ISSN
2375-2548
DOI
10.1126/sciadv.abd3865
URI
http://hdl.handle.net/10203/281117
Appears in Collection
BiS-Journal Papers(저널논문)
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