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Enhancing and stabilization of cord blood regulatory T-cell suppressive function by human mesenchymal stem cell (MSC)-derived exosomes.
- Source :
-
Clinical & Experimental Immunology . Jun2022, Vol. 208 Issue 3, p255-267. 13p. - Publication Year :
- 2022
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CORD blood
*MESENCHYMAL stem cells
*HUMAN stem cells
*EXOSOMES
*REGULATORY T cells
Subjects
Details
- Language :
- English
- ISSN :
- 00099104
- Volume :
- 208
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Clinical & Experimental Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 160116889
- Full Text :
- https://doi.org/10.1093/cei/uxac035