Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China.
Sci Rep. 2016 Dec 5;6:37566. doi: 10.1038/srep37566.
Human UC-MSCs are regarded as an attractive alternative to BM-MSCs for clinical applications due to their easy preparation, higher proliferation and lower immunogenicity. However, the mechanisms underlying immune suppression by UC-MSCs are still unclear. We studied the mechanism of inhibition by UC-MSCs during the differentiation of monocytes into DCs and focused on the specific source and the role of the involved cytokines. We found that UC-MSCs suppressed monocyte differentiation into DCs and instructed monocytes towards other cell types, with clear decreases in the expression of co-stimulatory molecules, in the secretion of inflammatory factors and in allostimulatory capacity. IL6, HGF and IL10 might be involved in this process because they were detected at higher levels in a coculture system. UC-MSCs produce IL-6 and HGF, and neutralization of IL-6 and HGF reversed the suppressive effect of UC-MSCs. IL10 was not produced by UC-MSCs but was exclusively produced by monocytes after exposure to UC-MSCs, IL-6 or HGF. In summary, we found that the UC-MSC-mediated inhibitory effect was dependent on IL6 and HGF secreted by UC-MSCs and that this effect induced monocyte-derived cells to produce IL10, which might indirectly strengthen the suppressive effect of UC-MSCs.
人 UC-MSCs 因其易于制备、增殖能力较强和免疫原性较低，被认为是 BM-MSCs 的一种有吸引力的替代物，可用于临床应用。然而，UC-MSCs 抑制免疫的机制尚不清楚。我们研究了 UC-MSCs 在单核细胞向 DC 分化过程中抑制作用的机制，重点研究了涉及的细胞因子的特定来源和作用。我们发现 UC-MSCs 抑制单核细胞向 DC 的分化，并指导单核细胞向其他细胞类型分化，共刺激分子的表达、炎症因子的分泌和同种刺激能力均明显降低。IL6、HGF 和 IL10 可能参与了这一过程，因为在共培养系统中检测到它们的水平升高。UC-MSCs 产生 IL-6 和 HGF，中和 IL-6 和 HGF 可逆转 UC-MSCs 的抑制作用。UC-MSCs 不产生 IL10，而是在暴露于 UC-MSCs、IL-6 或 HGF 后由单核细胞特异性产生。总之，我们发现 UC-MSC 介导的抑制作用依赖于 UC-MSCs 分泌的 IL6 和 HGF，并且这种作用诱导单核细胞来源的细胞产生 IL10，这可能间接增强 UC-MSCs 的抑制作用。
