한빛사논문
- 조회344
Sunyoung Jung1,2,10, Sunho Lee1,2,10, Hyun Je Kim2,3,4,5,10, Sueon Kim1, Ji Hwan Moon6, Hyunwoo Chung1, Seong-Jun Kang1,2 and Chung-Gyu Park1,2,3,7,8,9
1Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 03080, Korea.
2Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
3Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul 03080, Korea.
4Seoul National University Hospital, Seoul, Korea.
5Transplantation Research Institute, Seoul National University College of Medicine, Seoul 110-799, Korea.
6Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
7Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
8BK21Plus Biomedical Science Project, Seoul National University College of Medicine, Seoul 03080, Korea.
9Biomedical Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
10These authors contributed equally: Sunyoung Jung, Sunho Lee, Hyun Je Kim.
Corresponding author : Correspondence to Chung-Gyu Park.
Abstract
Mesenchymal stem cell (MSC)-derived small extracellular vesicles (MSC-sEVs) are known to exert immunosuppressive functions. This study showed that MSC-sEVs specifically convert T helper 17 (Th17) cells into IL-17 low-producer (ex-Th17) cells by degrading RAR-related orphan receptor γt (RORγt) at the protein level. In experimental autoimmune encephalomyelitis (EAE)-induced mice, treatment with MSC-sEVs was found to not only ameliorate clinical symptoms but also to reduce the number of Th17 cells in draining lymph nodes and the central nervous system. MSC-sEVs were found to destabilize RORγt by K63 deubiquitination and deacetylation, which was attributed to the EP300-interacting inhibitor of differentiation 3 (Eid3) contained in the MSC-sEVs. Small extracellular vesicles isolated from the Eid3 knockdown MSCs by Eid3-shRNA failed to downregulate RORγt. Moreover, forced expression of Eid3 by gene transfection was found to significantly decrease the protein level of RORγt in Th17 cells. Altogether, this study reveals the novel immunosuppressive mechanisms of MSC-sEVs, which suggests the feasibility of MSC-sEVs as an attractive therapeutic tool for curing Th17-mediated inflammatory diseases.
논문정보
- Research article
- 2023년 03월 (BRIC 등록일 2023-06-02)
- 국내 연구진
- 의약학 > 면역의학
관련 웨비나
![중간엽 줄기세포 유래 세포외 소포체에 의한 Th17 세포의 탈분화 연구 [Exp. Mol. Med.]](/upload/board/files/onseminar/thumb/thumb_0000605.png)
학술웨비나
중간엽 줄기세포 유래 세포외 소포체에 의한 Th17 세포의 탈분화 연구 [Exp. Mol. Med.] 중간엽 줄기세포(MSC) 유래 세포외 소포체(MSC-sEV)는 면역 억제 기능을 발휘하는 것으로 알려져 있다. 본 연구는 MSC-sEVs가 RORgt를 단백질 수준에서 분해하여 Th17 세포를 IL-17 저생산 (ex-Th17) 세포로 특이적으로 변환하는 것을 보여주었다. 또한, EAE 유도 생쥐에서 MSC-sEVs를 사용한 치료를 통해 임상 증상을 개선할 뿐만 아니라 림프절 및 중추신경계에서 Th17 세포의 수를 감소시키는 것을 확인하였다. MSC-sEVs는 K63 deubiquitination과 deacetylation을 통해 RORγt를 불안정하게 함을 확인하였으며, 이는 MSC-sEV에 포함된 Eid3로부터 기인하였음을 확인하였다. 전체적으로, 본 연구는 MSC-sEVs의 새로운 면역 억제 메커니즘을 밝혀내었으며, 이는 Th17 매개 염증성 질환 치료제로써의 MSC-sEVs의 실현 가능성을 제시하였다.- 정선영(서울대학교)
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