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Dendritic cells originating exosomal miR-193b-3p induces regulatory T cells to alleviate liver transplant rejection.
- Source :
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International immunopharmacology [Int Immunopharmacol] 2023 Jan; Vol. 114, pp. 109541. Date of Electronic Publication: 2022 Dec 21. - Publication Year :
- 2023
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Abstract
- Background: Exosomes exert considerable influence in mediating regulatory T (Treg) cells differentiation, which attach great importance to attenuating acute cellular rejection after liver transplantation (LT). And, miRNAs are known to play essential roles in cell-cell communication delivered by exosomes. However, the function of exosomal miRNAs in regulating Treg cells after LT remains unknown. Here, we performed an expression profiling analysis of exosome-miRNAs from human plasma after LT and investigated their immunoregulatory effects on Treg cells.<br />Methods: Fifty-eight LT patients and nine donors were included in this report. miRNA profiles in plasma exosomes were analyzed using next-generation sequencing. Flow cytometry, HE and multiplex immunofluorescent staining were used to identify Treg cells in the liver and peripheral blood. A lentiviral vector system was used to overexpress miR-193b-3p in dendritic cells (DCs), and exosomes isolated from these transfected cells were co-cultured with spleen lymphocytesin vitro. A quantitative Real-time PCR and enzyme-linked immunosorbent assay were used to detect the expression of cytokines.<br />Results: Treg cell infiltration was increased in the liver along with Th17 and CD8+ T cell, and it was down-regulated in peripheral blood in the acute rejection group. High-throughput sequencing revealed that miR-193b-3p was markedly up-regulated in plasma exosomes of non-rejection LT patients. The NLRP3 inflammasome was screened as a target for miR-193b-3p based on target prediction and functional enrichment analyses. Exosomal miR-193b-3p derived from DCs increased Treg cells as demonstrated in vitro. miR-193b-3p overexpression down-regulated NLRP3 as well as the inflammatory cytokines IL-1β and IL-17A while increasing levels of the cytokines IL-10 and TGF-β.<br />Conclusion: DC derived exosomal miR-193b-3p promoted Treg cells by inhibiting NLRP3 expression. These findings not only provide a new perspective on the mechanisms, but also hold great promise for the treatment or prevention of liver allograft rejection.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2022 Elsevier B.V. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 114
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 36700764
- Full Text :
- https://doi.org/10.1016/j.intimp.2022.109541