| First Author | Sheller-Miller S | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 4 | PubMed ID | 33523942 |
| Mgi Jnum | J:380508 | Mgi Id | MGI:8279106 |
| Doi | 10.1126/sciadv.abd3865 | Citation | Sheller-Miller S, et al. (2021) Exosomal delivery of NF-kappaB inhibitor delays LPS-induced preterm birth and modulates fetal immune cell profile in mouse models. Sci Adv 7(4) |
| abstractText | Accumulation of immune cells and activation of the pro-inflammatory transcription factor NF-kappaB in feto-maternal uterine tissues is a key feature of preterm birth (PTB) pathophysiology. Reduction of the fetal inflammatory response and NF-kappaB activation are key strategies to minimize infection-associated PTB. Therefore, we engineered extracellular vesicles (exosomes) to contain an NF-kappaB inhibitor, termed super-repressor (SR) IkappaBalpha. 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. |
