Exosomes derived from LPS-stimulated human thymic mesenchymal stromal cells enhance inflammation via thrombospondin-1.
Exosomes derived from LPS-stimulated human thymic mesenchymal stromal cells enhance inflammation via thrombospondin-1.
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源自LPS刺激的人胸腺间充质基质细胞的外泌体通过血小板反应蛋白-1增强炎症
DOI：
10.1042/bsr20203573
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发表时间：
2021-10-29
影响因子：
4
通讯作者：
Du Y
中科院分区：
文献类型：
--
作者：
Li Q;Li J;Sun L;Sun Y;Zhao F;Liu P;Peng X;Xuan X;Li Y;Wang P;Tan C;Du Y
免疫细胞介导的炎症反应直接或间接受间充质基质细胞（MSC）的调节。越来越多的证据表明，血小板反应蛋白-1（TSP-1）在炎症反应中高度表达。本研究分离鉴定了人胸腺间充质基质细胞（tMSCs），并检测了TSP-1的表达。我们发现tMSCs表达TSP-1，Poly（I：C）或LPS处理促进TSP-1的表达。此外，我们分离并鉴定了源自tMSC（MEX）的外来体。值得注意的是，来自LPS预处理的tMSCs的exosomes（MEXsLPS）促进巨噬细胞向M1样表型的极化和IL-6、TNF-α的分泌以及CD 4 +T细胞向Th 17细胞的促炎分化。在沉默tMSC中TSP-1的表达后，MEXsLPS的促炎作用被抑制。因此，这些发现揭示了TSP-1是MEXsLPS促炎调节中的主要因子。
Inflammatory response mediated by immune cells is either directly or indirectly regulated by mesenchymal stromal cells (MSCs). Accumulating evidence suggests that thrombospondin-1 (TSP-1) is highly expressed in response to inflammation. In this work, we isolated and identified human thymic mesenchymal stromal cells (tMSCs) and detected the expression of TSP-1. We found that tMSCs expressed TSP-1 and Poly (I:C) or LPS treatment promoted the expression of TSP-1. Further, we isolated and identified exosomes originating from tMSCs (MEXs). Notably, exosomes derived from LPS-pretreated tMSCs (MEXsLPS) promoted the polarization of macrophages to M1-like phenotype and IL-6, TNF-α secretion as well as the pro-inflammatory differentiation of CD4+T cells into Th17 cells. Upon silencing the expression of TSP-1 in tMSCs, the pro-inflammatory effects of MEXsLPS were suppressed. Therefore, these findings uncovered TSP-1 as the principal factor in MEXsLPS pro-inflammatory regulation.