Umbilical Cord-derived Mesenchymal Stem Cells Instruct Monocytes Towards an IL10-producing Phenotype by Secreting IL6 and HGF.
Umbilical Cord-derived Mesenchymal Stem Cells Instruct Monocytes Towards an IL10-producing Phenotype by Secreting IL6 and HGF.
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脐带间充质干细胞通过分泌 IL6 和 HGF 指导单核细胞产生 IL10 的表型。
DOI：
10.1038/srep37566
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发表时间：
2016-12-05
影响因子：
4.6
通讯作者：
Yang Y
中科院分区：
文献类型：
--
作者：
Deng Y;Zhang Y;Ye L;Zhang T;Cheng J;Chen G;Zhang Q;Yang Y
人UC-MSCs因其制备简单、增殖能力强、免疫原性低等优点，被认为是bmmscs在临床应用中的一个有吸引力的替代品。然而，UC-MSCs免疫抑制的机制尚不清楚。我们研究了UC-MSCs在单核细胞向dc分化过程中的抑制机制，并重点研究了其特异性来源和相关细胞因子的作用。我们发现UC-MSCs抑制单核细胞向dc分化，并指示单核细胞向其他细胞类型分化，同时明显降低共刺激分子的表达、炎症因子的分泌和异源刺激能力。IL6、HGF和IL10可能参与了这一过程，因为它们在共培养系统中被检测到较高的水平。UC-MSCs产生IL-6和HGF， IL-6和HGF的中和逆转了UC-MSCs的抑制作用。il - 10不是由UC-MSCs产生的，而是暴露于UC-MSCs、IL-6或HGF后的单核细胞完全产生的。综上所述，我们发现UC-MSCs介导的抑制作用依赖于UC-MSCs分泌的IL6和HGF，这种作用诱导单核细胞源性细胞产生IL10，这可能间接增强了UC-MSCs的抑制作用。
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.
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