Defining mesenchymal stem/stromal cell-induced myeloid-derived suppressor cells using single-cell transcriptomics.
Mol Ther
; 32(6): 1970-1983, 2024 Jun 05.
Article
em En
| MEDLINE
| ID: mdl-38627968
ABSTRACT
Mesenchymal stem/stromal cells (MSCs) modulate the immune response through interactions with innate immune cells. We previously demonstrated that MSCs alleviate ocular autoimmune inflammation by directing bone marrow cell differentiation from pro-inflammatory CD11bhiLy6ChiLy6Glo cells into immunosuppressive CD11bmidLy6CmidLy6Glo cells. Herein, we analyzed MSC-induced CD11bmidLy6Cmid cells using single-cell RNA sequencing and compared them with CD11bhiLy6Chi cells. Our investigation revealed seven distinct immune cell types including myeloid-derived suppressor cells (MDSCs) in the CD11bmidLy6Cmid cells, while CD11bhiLy6Chi cells included mostly monocytes/macrophages with a small cluster of neutrophils. These MSC-induced MDSCs highly expressed Retnlg, Cxcl3, Cxcl2, Mmp8, Cd14, and Csf1r as well as Arg1. Comparative analyses of CSF-1RhiCD11bmidLy6Cmid and CSF-1RloCD11bmidLy6Cmid cells demonstrated that the former had a homogeneous monocyte morphology and produced elevated levels of interleukin-10. Functionally, these CSF-1RhiCD11bmidLy6Cmid cells, compared with the CSF-1RloCD11bmidLy6Cmid cells, inhibited CD4+ T cell proliferation and promoted CD4+CD25+Foxp3+ Treg expansion in culture and in a mouse model of experimental autoimmune uveoretinitis. Resistin-like molecule (RELM)-γ encoded by Retnlg, one of the highly upregulated genes in MSC-induced MDSCs, had no direct effects on T cell proliferation, Treg expansion, or splenocyte activation. Together, our study revealed a distinct transcriptional profile of MSC-induced MDSCs and identified CSF-1R as a key cell-surface marker for detection and therapeutic enrichment of MDSCs.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Análise de Célula Única
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Células-Tronco Mesenquimais
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Células Supressoras Mieloides
Limite:
Animals
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Humans
Idioma:
En
Revista:
Mol Ther
/
Mol. ther
/
Molecular therapy
Assunto da revista:
BIOLOGIA MOLECULAR
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TERAPEUTICA
Ano de publicação:
2024
Tipo de documento:
Article