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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Extracellular Vesicles isolated from Mesenchymal Stromal Cells Modulate CD4(+) T Lymphocytes Toward a Regulatory Profile

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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
[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
Document type: Journal article
Source: CELLS; v. 9, n. 4 APR 2020.
Web of Science Citations: 0

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)

FAPESP's process: 17/05264-7 - Cell metabolism, microbiota and immune system: new paradigms in renal diseases physiopathology
Grantee:Niels Olsen Saraiva Câmara
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 18/08479-7 - Multi-user equipment approved in grant 17/05264-7: analisador de fluxo extracelular Seahorse XFe96
Grantee:Niels Olsen Saraiva Câmara
Support Opportunities: Multi-user Equipment Program
FAPESP's process: 14/07390-1 - Mesenchymal stromal cells derived microvesicles as inductors of immune tolerance
Grantee:Flavia Franco da Cunha
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 16/13029-5 - Role of miRNAs in regulatory T cell-mediated immunological tolerance
Grantee:Flavia Franco da Cunha
Support Opportunities: Scholarships abroad - Research Internship - Doctorate