期刊
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
卷 208, 期 3, 页码 255-267出版社
OXFORD UNIV PRESS
DOI: 10.1093/cei/uxac035
关键词
adoptive cellular immunotherapy; cord blood Tregs; mesenchymal stem cell-derived exosomes
类别
资金
- National key research and development program [2019YFA0110703]
- Project of Health and family planning commission of Hunan Province [20160125]
- National Natural Science Foundation of China [81201171, 81771827, 81971721]
- Hunan Provincial Science and Technology Department Major Project [2018SK1020]
Hucb-Tregs treated with MSC-CM or MSC-derived exosomes were more suppressive and resistant to inflammatory stimulation. MSC-derived exosomes could activate autophagy and JAK3-Stat5 signaling pathway to promote Treg survival and regulate FOXP3 expression. MSC-derived exosomes could be an effective strategy to improve the Tregs-based cell therapy landscape.
FOXP3(+) regulatory T cells (Tregs) are central to maintaining peripheral tolerance and immune homeostasis. They have the potential to be developed as a cellular therapy to treat various clinical ailments such as autoimmune disorders, inflammatory diseases and to improve transplantation outcomes. However, a major question remains whether Tregs can persist and exert their function effectively in a disease state, where a broad spectrum of inflammatory mediators could inactivate Tregs. In this study, we investigated the potential of mesenchymal stem cell (MSC)-derived exosomes to promote and sustain Tregs function. MSC-conditioned media (MSC-CM) cultured Tregs were more suppressive in both polyclonal and allogeneic responses and were resistant to inflammatory stimulation in vitro compared with the controls. A similar enhancement of Treg function was also observed by culturing Tregs with MSC-derived exosomes alone. The enhanced suppressive activity and stability of Treg cultured in MSC-CM was reduced when exosomes were depleted from MSC-CM. We identified that MSC-derived exosomes could upregulate the expression of LC3(II/I), phosphorylate Jak3 and Stat5 to promote Treg survival, and regulate FOXP3 expression in Tregs. Overall, our study demonstrates that MSC-derived exosomes are capable of enhancing Hucb-Tregs function and stability by activating autophagy and Stat5 signalling pathways. Our findings provide a strong rationale for utilizing MSC-derived exosomes as an effective strategy to enhance Treg function, and improve the overall Tregs-based cell therapy landscape. Hucb-Tregs treated with MSC-CM or MSC-derived exosomes were more suppressive and were resistant to inflammatory stimulation. MSC-derived exosomes could activate autophagy and JAK3-Stat5 signalling pathway to promote Treg survival, and regulate FOXP3 expression. MSC-derived exosomes could be an effective strategy to improve the Tregs-based cell therapy landscape.
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