间充质干细胞
促炎细胞因子
启动(农业)
生物
硼替佐米
免疫学
细胞因子
癌症研究
间质细胞
免疫系统
干细胞
炎症
细胞生物学
多发性骨髓瘤
植物
发芽
作者
Ha Young Park,Chae Eun Kim,Soung-Min Lee,Joo Mi Ahn,Eun Hye Yoon,Myung‐Chul Yoo,Jung‐Mi Kim,Jiyeon Back,Dae Hwi Park,Won Hee Jang,Byungsuk Kwon,Su‐Kil Seo
出处
期刊:Stem Cells
[Oxford University Press]
日期:2022-10-15
卷期号:41 (1): 64-76
被引量:7
标识
DOI:10.1093/stmcls/sxac075
摘要
Abstract Preconditioning of mesenchymal stem/stromal cells (MSCs) with the inflammatory cytokine IFN-γ enhances not only their immunosuppressive activity but also their expression of HLA and proinflammatory genes. We hypothesized that prevention of the upregulation of inflammatory cytokines and HLA molecules in IFN-γ-primed MSCs would render these cells more immunosuppressive and less immunogenic. In this study, we discovered the following findings supporting this hypothesis: (1) activated human T cells induced the expression of IDO1 in MSCs via IFN-γ secretion and those MSCs in turn inhibited T-cell proliferation in an AHR-dependent fashion; (2) there was no difference in the expression of IDO1 and HLA-DR in MSCs after priming with a low dose (25 IU/mL) versus a high dose (100 IU/mL) of IFN-γ; (3) the transient addition of bortezomib, a proteasome inhibitor, to culture MSCs after IFN-γ priming decreased the expression of HLA-DR, inflammatory cytokine genes and Vcam1 while increasing the expression of IDO1 and the production of L-kynurenine; finally, MSCs primed with a combination of a low dose of IFN-γ and bortezomib were more effective in inhibiting Th17-mediated idiopathic pneumonia syndrome (IPS) and chronic colitis than unprimed MSCs. Our results suggest that bortezomib significantly eliminates the unfavorable effects of IFN-γ priming of MSCs (increased expression of MHC molecules and inflammatory cytokines and cell aggregation genes) and simultaneously increases their immunosuppressive activity by upregulating IDO1. Taken together, our newly established MSC priming method may contribute to MSC-based cell therapy for inflammatory diseases.
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