Osteoarthritis Research Unit, Department of Medicine, University of Montreal Hospital Research Center (CRCHUM), 900 rue Saint-Denis, R11.424, Montreal, QC, H2X 0A9, Canada.
Laboratory of Cancer Biology and Molecular Immunology, Faculty of Sciences I, Lebanese University, Hadath, Lebanon.
Inflamm Res. 2019 Mar;68(3):203-213. doi: 10.1007/s00011-018-1205-0. Epub 2018 Nov 30.
The objective of the study is to uncover the influence of human bone marrow-derived mesenchymal stem cells (BM-MSCs) on the generation of Th17 lymphocytes in co-cultures of both BM-MSCs and T cells.
BM-MSCs, characterized according to the international society for cellular therapy (ISCT) criteria, were co-cultured with T cells isolated from peripheral blood. The expression levels of IL-17 receptor, RORγt and IL-23 receptor were evaluated using flow cytometry. The levels of cytokines involved in Th17 immunomodulation were measured using multiplex assay.
Inflammatory primed and non-primed BM-MSCs were co-cultured with either activated or non-activated T cells either at (1/80) and (1/5) ratio respectively.
MSC/T-cell ratio and inflammation significantly influenced the effect of BM-MSCs on the generation of Th17 lymphocytes. Cocultures of either primed or non-primed BM-MSCs with activated T cells significantly induced IL-17A-expressing lymphocytes. Interestingly, the expression of the transcription factor RORγt was significantly increased when compared to levels in activated T cells. Finally, both cell ratio and priming of BM-MSCs with cytokines substantially influenced the cytokine profile of BM-MSCs and T cells.
Our findings suggest that BM-MSCs significantly modulate the Th17 lymphocyte pathway in a complex manner.
本研究旨在揭示骨髓间充质干细胞(BM-MSCs)在 BM-MSCs 与 T 细胞共培养物中对 Th17 淋巴细胞生成的影响。
根据国际细胞治疗学会(ISCT)标准,对 BM-MSCs 进行特征鉴定,然后与外周血中分离的 T 细胞进行共培养。使用流式细胞术评估 IL-17 受体、RORγt 和 IL-23 受体的表达水平。使用多重分析测定法测量涉及 Th17 免疫调节的细胞因子水平。
将炎症激活和未激活的 BM-MSCs 分别以(1/80)和(1/5)的比例与激活或未激活的 T 细胞共培养。
MSC/T 细胞比例和炎症显著影响 BM-MSCs 对 Th17 淋巴细胞生成的影响。与激活的 T 细胞共培养的激活或未激活的 BM-MSCs 均可显著诱导表达 IL-17A 的淋巴细胞。有趣的是,与激活的 T 细胞相比,转录因子 RORγt 的表达显著增加。最后,细胞比例和 BM-MSCs 与细胞因子的预激活均显著影响 BM-MSCs 和 T 细胞的细胞因子谱。
我们的研究结果表明,BM-MSCs 以复杂的方式显著调节 Th17 淋巴细胞途径。