Abstract:
:Adipose-derived stem cells (ADSCs) are a type of multipotent mesenchymal stem cells with immunosuppressive capacities. However, the underlying mechanisms involved in the inhibitory effects of ADSCs on T cells are not completely elucidated. In this study, human peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3/CD28 antibody-coated beads were cultured with or without allogeneic ADSCs (ADSC-to-PBMC ratio, 1:5). Surface marker levels, violet-labeled cell proliferation, apoptosis, interferon-gamma (IFN-gamma) production, and nuclear factor-kappaB (NF-kappaB) phosphorylation of CD4+ and CD8+ T cells were detected using flow cytometry. It was observed that ADSCs significantly suppressed the proliferation and IFN-gamma production but enhanced apoptosis of both CD4+ and CD8+ T cells in T cell receptor (TCR)-stimulated PBMCs. The expressions of programmed death-ligand 1 (PD-L1) and galectin 9 (Gal-9) on ADSCs were significantly upregulated and induced during coculture with PBMCs. TCR-stimulated CD4+ and CD8+ T cells cultured with ADSCs had higher expression levels of programmed death-1 (PD-1) and T cell immunoglobulin and mucin-containing protein-3 (TIM-3) than those in cells cultured without ADSCs. Moreover, the suppressive effects of ADSCs on T cells in terms of proliferation and IFN-gamma production were significantly reversed in the presence of anti-PD-L1 and anti-Gal-9 antibodies. Importantly, the phosphorylation of NF-kappaB in CD4+ and CD8+ T cells cocultured with ADSCs was significantly inhibited, and this inhibition was significantly attenuated via the PD-L1 and Gal-9 blockades. In conclusion, human ADSCs perform immunoregulatory functions partially through the inhibition of NF-kappaB activation in T cells via the PD-L1/PD-1 and Gal-9/TIM-3 pathways, which provide new insights into the mechanism of human ADSC-mediated immunomodulation.
journal_name
Stem Cells Devjournal_title
Stem cells and developmentauthors
Zhou K,Guo S,Tong S,Sun Q,Li F,Zhang X,Qiao Y,Liang Gdoi
10.1089/scd.2018.0033subject
Has Abstractpub_date
2018-09-01 00:00:00pages
1191-1202issue
17eissn
1547-3287issn
1557-8534journal_volume
27pub_type
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journal_title:Stem cells and development
pub_type: 杂志文章
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journal_title:Stem cells and development
pub_type: 杂志文章
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journal_title:Stem cells and development
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journal_title:Stem cells and development
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journal_title:Stem cells and development
pub_type: 杂志文章
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journal_title:Stem cells and development
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journal_title:Stem cells and development
pub_type: 杂志文章
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journal_title:Stem cells and development
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doi:10.1089/scd.2008.0358
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journal_title:Stem cells and development
pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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journal_title:Stem cells and development
pub_type: 杂志文章
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journal_title:Stem cells and development
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journal_title:Stem cells and development
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journal_title:Stem cells and development
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journal_title:Stem cells and development
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pub_type: 杂志文章,评审
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