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Exp. Mol. Med., 20 January 2025 | https://doi.org/10.1038/s12276-024-01388-8
Exosome-based targeted delivery of NF-κB ameliorates age-related neuroinflammation in the aged mouse brain
Chae-Jeong Lee1,5, Seung Hyun Jang2,5, Jiwoo Lim1, Hyunju Park1, So-Hee Ahn3, Seon Young Park3, Hyangmi Seo3, Soo-Jin Song4, Jung-A Shin4, Chulhee Choi3, Heon Yung Gee2 and Youn-Hee Choi1
1Department of Physiology, Inflammation-Cancer Microenvironment Research Center, Ewha Womans University College of Medicine, Seoul 07804, Republic of Korea.
2Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
3ILIAS Biologics Inc., Daejeon 34014, Republic of Korea.
4Department of Anatomy, Ewha Womans University College of Medicine, Seoul 07804, Republic of Korea.
5These authors contributed equally: Chae-Jeong Lee, Seung Hyun Jang.
Corresponding authors
Correspondence to Chulhee Choi, Heon Yung Gee or Youn-Hee Choi.
1Department of Physiology, Inflammation-Cancer Microenvironment Research Center, Ewha Womans University College of Medicine, Seoul 07804, Republic of Korea.
2Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
3ILIAS Biologics Inc., Daejeon 34014, Republic of Korea.
4Department of Anatomy, Ewha Womans University College of Medicine, Seoul 07804, Republic of Korea.
5These authors contributed equally: Chae-Jeong Lee, Seung Hyun Jang.
Corresponding authors
Correspondence to Chulhee Choi, Heon Yung Gee or Youn-Hee Choi.
Abstract
Neuroinflammation, a significant contributor to various neurodegenerative diseases, is strongly associated with the aging process; however, to date, no efficacious treatments for neuroinflammation have been developed. In aged mouse brains, the number of infiltrating immune cells increases, and the key transcription factor associated with increased chemokine levels is nuclear factor kappa B (NF-κB). Exosomes are potent therapeutics or drug delivery vehicles for various materials, including proteins and regulatory genes, to target cells. In the present study, we evaluated the therapeutic efficacy of exosomes loaded with a nondegradable form of IκB (Exo-srIκB), which inhibits the nuclear translocation of NF-κB to suppress age-related neuroinflammation. Single-cell RNA sequencing revealed that these anti-inflammatory exosomes targeted macrophages and microglia, reducing the expression of inflammation-related genes. Treatment with Exo-srIκB also suppressed the interactions between macrophages/microglia and T and B cells in the aged brain. We demonstrated that Exo-srIκB successfully alleviates neuroinflammation by primarily targeting activated macrophages and partially modulating the functions of age-related interferon-responsive microglia in the brain. Thus, our findings highlight Exo-srIκB as a potential therapeutic agent for treating age-related neuroinflammation.
논문정보
- Research article
- 2025년 01월 (BRIC 등록일 2025-01-21)
- 국내 연구진
- 의약학 > 유전 및 유전체의학
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