Enhancing and stabilization of cord blood regulatory T-cell suppressive function by human mesenchymal stem cell (MSC)-derived exosomes
| Autor: | Juan Zhang, Xiaoqian Ma, Lu Cao, Xing He, Sang Li, Min Yang, Cejun Yang, Pengfei Rong, Shounan Yi, Kedar Ghimire, Xiangfeng Kong, Wei Wang |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Clin Exp Immunol |
| ISSN: | 1365-2249 0009-9104 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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