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Author(s):
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da Cunha, Flavia Franco
[1]
;
Andrade-Oliveira, Vinicius
[2]
;
de Almeida, Danilo Candido
[1]
;
da Silva, Tamiris Borges
[1]
;
de Souza Breda, Cristiane Naffah
[2]
;
Cruz, Mario Costa
[2]
;
Faquim-Mauro, Eliana L.
[3]
;
Cenedeze, Marcos Antonio
[1]
;
Hiyane, Meire Ioshie
[2]
;
Pacheco-Silva, Alvaro
[1, 4]
;
Cavinato, Regiane Aparecida
[1]
;
Torrecilhas, Ana Claudia
[5]
;
Saraiva Camara, Niels Olsen
[1, 2]
Total Authors: 13
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| Affiliation: | [1] Univ Fed Sao Paulo, Dept Nefrol, Rua Pedro Toledo 669, BR-04039032 Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Imunol, Ave Prof Lineu Prestes 1730, ICB IV, BR-05508000 Sao Paulo - Brazil
[3] Inst Butantan, Lab Imunopatol, Ave Vital Brasil 1500, BR-05503900 Sao Paulo - Brazil
[4] Hosp Israelita Albert Einstein, Ave Albert Einstein, BR-62705652 Sao Paulo - Brazil
[5] Univ Fed Sao Paulo, Dept Ciencias Farmaceut, Rua Sao Nicolau 210, BR-09913030 Sao Paulo - Brazil
Total Affiliations: 5
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| Document type: |
Journal article
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| Source: |
CELLS;
v. 9,
n. 4
APR 2020.
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| Web of Science Citations: |
0
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| Abstract |
Mesenchymal stromal cells (MSCs) can generate immunological tolerance due to their regulatory activity in many immune cells. Extracellular vesicles (EVs) release is a pivotal mechanism by which MSCs exert their actions. In this study, we evaluate whether mesenchymal stromal cell extracellular vesicles (MSC-EVs) can modulate T cell response. MSCs were expanded and EVs were obtained by differential ultracentrifugation of the supernatant. The incorporation of MSC-EVs by T cells was detected by confocal microscopy. Expression of surface markers was detected by flow cytometry or CytoFLEX and cytokines were detected by RT-PCR, FACS and confocal microscopy and a miRNA PCR array was performed. We demonstrated that MSC-EVs were incorporated by lymphocytes in vitro and decreased T cell proliferation and Th1 differentiation. Interestingly, in Th1 polarization, MSC-EVs increased Foxp3 expression and generated a subpopulation of IFN-gamma(+)/Foxp3(+)T cells with suppressive capacity. A differential expression profile of miRNAs in MSC-EVs-treated Th1 cells was seen, and also a modulation of one of their target genes, TGFbR2. MSC-EVs altered the metabolism of Th1-differentiated T cells, suggesting the involvement of the TGF-beta pathway in this metabolic modulation. The addition of MSC-EVs in vivo, in an OVA immunization model, generated cells Foxp3(+). Thus, our findings suggest that MSC-EVs are able to specifically modulate activated T cells at an alternative regulatory profile by miRNAs and metabolism shifting. (AU) |
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| FAPESP's process: |
17/05264-7 - Cell metabolism, microbiota and immune system: new paradigms in renal diseases physiopathology
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| Grantee: | Niels Olsen Saraiva Câmara |
| Support type: |
Research Projects - Thematic Grants
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| FAPESP's process: |
18/08479-7 - Multi-user equipment approved in grant 17/05264-7: analisador de fluxo extracelular Seahorse XFe96
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| Grantee: | Niels Olsen Saraiva Câmara |
| Support type: |
Multi-user Equipment Program
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| FAPESP's process: |
14/07390-1 - Mesenchymal stromal cells derived microvesicles as inductors of immune tolerance
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| Grantee: | Flavia Franco da Cunha |
| Support type: |
Scholarships in Brazil - Doctorate
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| FAPESP's process: |
16/13029-5 - Role of miRNAs in regulatory T cell-mediated immunological tolerance
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| Grantee: | Flavia Franco da Cunha |
| Support type: |
Scholarships abroad - Research Internship - Doctorate
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