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

Samantha Sheller-Miller, Enkhtuya Radnaa, Jae Kwang Yoo, Eunsoo Kim, Kyungsun Choi, Youngeun Kim, Yuna Kim, Lauren Richardson, Chulhee Choi, Ramkumar Menon

Research output: Contribution to journalArticlepeer-review

Abstract

Accumulation of immune cells and activation of the pro-inflammatory transcription factor NF-κB in feto-maternal uterine tissues is a key feature of preterm birth (PTB) pathophysiology. Reduction of the fetal inflammatory response and NF-κB activation are key strategies to minimize infection-associated PTB. Therefore, we engineered extracellular vesicles (exosomes) to contain an NF-κB inhibitor, termed super-repressor (SR) IκBα. Treatment with SR exosomes (1 × 1010 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.

Original languageEnglish (US)
Article numbereabd3865
JournalScience Advances
Volume7
Issue number4
DOIs
StatePublished - Jan 22 2021
Externally publishedYes

ASJC Scopus subject areas

  • General

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