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Sci. Adv., Jul 04 2025, 11 (27) | https://doi.org/10.1126/sciadv.adp0467
Single-cell analysis of the decidua unveils the mechanism of anti-inflammatory exosomes for chorioamnionitis in nonhuman primates
Seung Hyun Jang 1, Hojun Choi 2, Eun Mi Lee 3 4, Seung-Bin Yoon 5, Hye-Jung Kim 2 6, Cheolhyoung Park 2, Jae Kyung Won 7, Seung Han Shin 8, Ji-Su Kim 5 *, Chan-Wook Park 3 4 *, Heon Yung Gee 1 *, Chulhee Choi 2 *
1Department of Pharmacology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea.
2ILIAS Biologics Inc., Daejeon, Korea.
3Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
4Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University, Seoul, 03087, Korea.
5Primate Resources Center (PRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup-si, Jeollabuk-do, Korea.
6Korea Institute of Ceramic Engineering and Technology, Cheongju, 28160, Korea.
7Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
8Department of Pediatrics, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
2ILIAS Biologics Inc., Daejeon, Korea.
3Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
4Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University, Seoul, 03087, Korea.
5Primate Resources Center (PRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup-si, Jeollabuk-do, Korea.
6Korea Institute of Ceramic Engineering and Technology, Cheongju, 28160, Korea.
7Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
8Department of Pediatrics, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
*Corresponding authors: correspondence to Ji-Su Kim, Chan-Wook Park, Heon Yung Gee or Chulhee Choi
Abstract
The effectiveness of exosomes engineered to carry a dominantly active variant of inhibitor α of nuclear factor κB (NF-κB) (IκBα), super-repressor IκB (srIκB), that inhibits the expression of NF-κB in various animal models of inflammatory diseases has been demonstrated. In this study, we used a lipopolysaccharide (LPS)-induced chorioamnionitis model in pregnant nonhuman primates to explore the therapeutic potential and mode of action of srIκB-loaded exosomes (Exo-srIκBs). Intraamniotic injection of LPS induced infiltration of BCL2A1-positive neutrophils and CD68-positive macrophages in the extraplacental membranes, causing fetal lung injury. Conversely, administration of Exo-srIκB via intraamniotic and intravenous routes (6.9 × 1010 and 4 × 1011 particle numbers, respectively) ameliorated these effects. Single-cell RNA sequencing of the decidua and bulk RNA sequencing of the choriodecidua highlighted that Exo-srIκB treatment mitigated LPS-induced inflammatory pathways, particularly in macrophages, leading to a cascade effect on neutrophils through NF-κB signaling inhibition. These findings underscore the potential of Exo-srIκB as a therapeutic strategy for chorioamnionitis.
논문정보
- Research article
- 2025년 07월 (BRIC 등록일 2025-07-04)
- 국내 연구진
- 의약학 > 의약학 기타
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