Integrated Analysis of Transcriptome and Secretome From Umbilical Cord Mesenchymal Stromal Cells Reveal New Mechanisms for the Modulation of Inflammation and Immune Activation.
Integrated Analysis of Transcriptome and Secretome From Umbilical Cord Mesenchymal Stromal Cells Reveal New Mechanisms for the Modulation of Inflammation and Immune Activation.
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来自脐带间充质基质细胞的转录组和分泌组的综合分析揭示了调节炎症和免疫激活的新机制。
DOI：
10.3389/fimmu.2020.575488
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发表时间：
2020
影响因子：
7.3
通讯作者：
Salguero G
中科院分区：
文献类型：
--
作者：
Cruz-Barrera M;Flórez-Zapata N;Lemus-Diaz N;Medina C;Galindo CC;González-Acero LX;Correa L;Camacho B;Gruber J;Salguero G
间充质基质细胞 (MSC) 已用于 800 多项临床试验，在移植医学和慢性炎症性疾病领域取得了令人鼓舞的结果。如今，脐带 (UC) 衍生的 MSC 是用于临床目的的第二大来源，主要是因为其易于获取和卓越的免疫调节作用。尽管免疫抑制活性的潜在分子机制尚未完全了解，但过去十年的研究强烈表明 MSC 介导的益处与分泌蛋白组网络的激活密切相关。尽管如此，最近的研究结果也指出细胞因子独立机制是间充质干细胞介导的免疫调节的关键因素。在这里，我们使用植物血凝素或抗 CD3/CD28 处理的人外周血单核细胞与 UC-MSC 以细胞间相互作用或细胞接触独立的形式建立了强大的体外免疫测定，并进行了整合的转录组和分泌组分析，以剖析驱动 UC-MSC 介导的免疫调节的分子途径。在炎症刺激下，分泌组的多参数分析使我们确定了与诱导 MSC 重编程巨噬细胞和 T 细胞亚群相关的细胞因子/趋化因子表达模式，最终导致免疫抑制。炎症挑战下的 UC-MSC 转录组分析可以鉴定出 47 个差异表达基因，包括趋化因子、抗炎和促炎细胞因子以及在 UC-MSC 免疫抑制分泌组中发现的粘附分子，包括新的候选可溶性 IL-2R。这项研究使我们能够追踪免疫抑制期间功能激活的 UC-MSC，并为探索 UC-MSC 参与免疫控制的新途径提供了机会。我们建议，已确定的免疫调节分子和途径有可能转化为临床环境，以提高 UC-MSC 治疗的质量和疗效。
Mesenchymal stromal cells (MSC) have been used in over 800 clinical trials with encouraging results in the field of transplant medicine and chronic inflammatory diseases. Today, Umbilical Cord (UC)-derived MSC are the second leading source used for clinical purposes, mainly due to its easy access and superior immune modulatory effects. Although the underlying molecular mechanisms of immune suppressive activities have not been fully understood, research over the last decade strongly suggests that MSC-mediated benefits are closely related to activation of secretome networks. Nevertheless, recent findings also point to cytokine-independent mechanisms as key players of MSC-mediated immune modulation. Here, we set up a robust in vitro immune assay using phytohemagglutinin- or anti-CD3/CD28-treated human peripheral blood mononuclear cells in cell-to-cell interaction or in cell-contact independent format with UC-MSC and conducted integrated transcriptome and secretome analyses to dissect molecular pathways driving UC-MSC-mediated immune modulation. Under inflammatory stimuli, multiparametric analyses of the secretome led us to identify cytokine/chemokine expression patterns associated with the induction of MSC-reprogrammed macrophages and T cell subsets ultimately leading to immune suppression. UC-MSC transcriptome analysis under inflammatory challenge allowed the identification of 47 differentially expressed genes, including chemokines, anti- and pro-inflammatory cytokines and adhesion molecules found also in UC-MSC-immunosupressive secretomes, including the novel candidate soluble IL-2R. This study enabled us to track functionally activated UC-MSC during immune suppression and opened an opportunity to explore new pathways involved in immunity control by UC-MSC. We propose that identified immunomodulatory molecules and pathways could potentially be translated into clinical settings in order to improve UC-MSC-therapy quality and efficacy.
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影响因子：
6
作者：
Khoury, Oula;Atala, Anthony;Murphy, Sean, V
通讯作者：
Murphy, Sean, V
影响因子：
2.6
作者：
Kim, Jaehyup;Hematti, Peiman
通讯作者：
Hematti, Peiman
影响因子：
5.2
作者：
Chiossone, Laura;Conte, Romana;Bottino, Cristina
通讯作者：
Bottino, Cristina
影响因子：
24.1
作者：
Cho, Kyung-Ah;Lee, Jun-Kyu;Ryu, Kyung-Ha
通讯作者：
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影响因子：
4.8
作者：
Corsello, Tiziana;Amico, Giandomenico;La Rocca, Giampiero
通讯作者：
La Rocca, Giampiero