오주연 (서울대학교병원)

한빛사논문

조회364

서울대학교병원

CV File 191 kb

Mol. Ther., April 15, 2024 | https://doi.org/10.1016/j.ymthe.2024.04.026 Defining Mesenchymal Stem/Stromal Cell-Induced Myeloid-Derived Suppressor Cells Using Single-Cell Transcriptomics

Hyun Ju Lee,¹ Yoo Rim Choi,¹ Jung Hwa Ko,¹Jin Suk Ryu¹ and Joo Youn Oh^1,2*

¹Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea

²Department of Ophthalmology, Seoul National University College of Medicine, 103 Daehak12 ro, Jongno-gu, Seoul 03080, Korea

^*Correspondence should be addressed to Joo Youn Oh, MD, PhD

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 BM 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 7 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 IL-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. 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.

논문정보

형식Research article
게재일2024년 04월 (BRIC 등록일 2024-04-17)
연구진국내 연구진
분야 의약학 > 응용의학

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