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

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Autor(es):
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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]
Número total de Autores: 13
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: CELLS; v. 9, n. 4 APR 2020.
Citações Web of Science: 0
Resumo

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)

Processo FAPESP: 17/05264-7 - Metabolismo celular, microbiota e sistema imune: novos paradigmas na fisiopatologia das doenças renais
Beneficiário:Niels Olsen Saraiva Câmara
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 18/08479-7 - EMU concedido no processo 2017/05264-7: analisador de fluxo extracelular Seahorse XFe96
Beneficiário:Niels Olsen Saraiva Câmara
Linha de fomento: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
Processo FAPESP: 14/07390-1 - Microvesículas derivadas de células estromais mesenquimais como indutoras de tolerância imunológica
Beneficiário:Flavia Franco da Cunha
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 16/13029-5 - Papel dos miRNAs na tolerância imunológica mediada por células T reguladoras
Beneficiário:Flavia Franco da Cunha
Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Doutorado