Department of Clinical Immunology, Xijing Hospital, The Fourth Military Medical University, No. 127 West Changle Road, Xi'an, Shaanxi Province, People's Republic of China.
Department of Cell Biology, Fourth Military Medical University, Xi'an, China.
Sci Rep. 2018 Jan 11;8(1):427. doi: 10.1038/s41598-017-18693-0.
Mesenchymal stem cells (MSCs) are multi-potent cells that are self-renewable and possess the potential to differentiate into multiple lineages. Several studies demonstrated that MSCs could regulate a Th17/Treg balance and could be a potential therapeutic target for Rheumatoid Arthritis (RA). A20 is highly expressed in many cell types after the stimulation of TNF-α, where it may inhibit pro-inflammatory cytokine secretion. However, the expression of A20 in BM-MSCs in RA is not fully understood. In our study, we found that A20 was decreased in RA patients' bone marrow MSCs (BM-MSCs), and with more IL-6 secretion, the balance of Th17/Treg was broken. In CIA mice, we found a moderate A20 decrease in mice MSCs as compared with those of control group in mRNA and protein levels. However, the IL-6 expression was increased. After umbilical cord MSCs treatment, A20 and IL-6 expressions were equal to the control group. Thus, our study indicates that loss of A20 in MSCs regulates the Th17/Treg balance in RA and the regulatory role of A20 in pro-inflammatory IL-6 production could be a potential target for the transfer of MSCs in RA adoptive therapy.
间充质干细胞（MSCs）是多能细胞，具有自我更新和分化为多个谱系的潜力。几项研究表明，MSCs 可以调节 Th17/Treg 平衡，可能成为类风湿关节炎（RA）的潜在治疗靶点。A20 在 TNF-α刺激后在许多细胞类型中高度表达，其中它可能抑制促炎细胞因子的分泌。然而，RA 患者骨髓间充质干细胞（BM-MSCs）中 A20 的表达尚不完全清楚。在我们的研究中，我们发现 A20 在 RA 患者的骨髓间充质干细胞（BM-MSCs）中减少，并且随着更多的 IL-6 分泌，Th17/Treg 的平衡被打破。在 CIA 小鼠中，与对照组相比，我们发现小鼠 MSCs 中的 A20 表达在 mRNA 和蛋白质水平上均降低。然而，IL-6 的表达增加。在脐带间充质干细胞治疗后，A20 和 IL-6 的表达与对照组相当。因此，我们的研究表明，MSCs 中 A20 的缺失调节 RA 中的 Th17/Treg 平衡，A20 对促炎 IL-6 产生的调节作用可能成为 RA 过继治疗中 MSC 转移的潜在靶点。
