| Autor: |
Henao Agudelo, Juan S., Braga, Tarcio T., Amano, Mariane T., Cenedeze, Marcos A., Cavinato, Regiane A., Peixoto-Santos, Amandda R., Muscará, Marcelo N., Teixeira, Simone A., Cruz, Mario C., Castoldi, Angela, Sinigaglia-Coimbra, Rita, Pacheco-Silva, Alvaro, de Almeida, Danilo C., Camara, Niels Olsen Saraiva |
| Předmět: |
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| Zdroj: |
Frontiers in Immunology; 7/31/2017, p1-15, 15p |
| Abstrakt: |
Mesenchymal stromal cells (MSCs) are multipotent cells with abilities to exert immunosuppressive response promoting tissue repair. Studies have shown that MSCs can secrete extracellular vesicles (MVs-MSCs) with similar regulatory functions to the parental cells. Furthermore, strong evidence suggesting that MVs-MSCs can modulate several immune cells (i.e., Th1, Th17, and Foxp3+ T cells). However, their precise effect on macrophages (MΦs) remains unexplored. We investigated the immunoregulatory effect of MVs-MSCs on activated M1-MΦs in vitro and in vivo using differentiated bone marrow MΦs and an acute experimental model of thioglycollate-induced peritonitis, respectively. We observed that MVs-MSCs shared surface molecules with MSCs (CD44, CD105, CD90, CD73) and expressed classical microvesicle markers (Annexin V and CD9). The in vitro treatment with MVs-MSCs exerted a regulatory-like phenotype in M1-MΦs, which showed higher CD206 level and reduced CCR7 expression. This was associated with decreased levels of inflammatory molecules (IL-1β, IL-6, nitric oxide) and increased immunoregulatory markers (IL-10 and Arginase) in M1-MΦs. In addition, we detected that MVs-MSCs promoted the downregulation of inflammatory miRNAs (miR-155 and miR-21), as well as, upregulated its predicted target gene SOCS3 in activated M1-MΦs. In vivo MVs-MSCs treatment reduced the MΦs infiltrate in the peritoneal cavity inducing a M2-like regulatory phenotype in peritoneal MΦs (higher arginase activity and reduced expression of CD86, iNOS, IFN-γ, IL-1β, TNF-a, IL-1a, and IL-6 molecules). This in vivo immunomodulatory effect of MVs-MSCs on M1-MΦs was partially associated with the upregulation of CX3CR1 in F4/80+/Ly6C+/CCR2+ MΦs subsets. In summary, our findings indicate that MVs-MSCs can modulate an internal program in activated MΦs establishing an alternative regulatory-like phenotype. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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