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

Cells

Ana Claudia Torrecilhas¹  Cristiane Naffah de Souza Breda²  Vinicius Andrade-Oliveira²  Mario Costa Cruz²  Meire Ioshie Hiyane²  Marcos Antonio Cenedeze³  Danilo Candido de Almeida³  Alvaro Pacheco-Silva³  Niels Olsen Saraiva Câmara³  Flavia Franco da Cunha³  Regiane Aparecida Cavinato³  Tamiris Borges da Silva³  Eliana L. Faquim-Mauro⁴ 

[1] Departamento de Ciências Farmacêuticas, UNIFESP, Rua São Nicolau, 210, Diadema 09913-030, São Paulo, Brazil;Departamento de Imunologia, USP, Avenida Prof. Lineu Prestes, 1730, ICB IV, São Paulo 05508-000, Brazil;Departamento de Nefrologia, UNIFESP, Rua Pedro de Toledo, 669, São Paulo 04039-032, Brazil;Laboratório de Imunopatologia, Instituto Butantan, Av. Vital Brasil, 1500, São Paulo 05503-900, Brazil;

关键词: mesenchymal stromal cells;    extracellular vesicles;    Th1 polarization;    miRNA;    metabolism;   

DOI  :  10.3390/cells9041059

来源: DOAJ

【 摘 要 】

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-γ⁺/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-β 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.

【 授权许可】

Unknown