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.

中文翻译：

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源自 LPS 的外泌体刺激人类胸腺间充质基质细胞通过 Thrombospondin-1 增强炎症。

由免疫细胞介导的炎症反应直接或间接由间充质基质细胞 (MSCs) 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。在这项工作中，我们分离并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 处理促进了 TSP-1 的表达。此外，我们分离并鉴定了源自 tMSCs (MEXs) 的外泌体。值得注意的是，来自 LPS 预处理的 tMSC (MEXsLPS) 的外泌体促进巨噬细胞极化为 M1 样表型和 IL-6、TNF-α 分泌以及 CD4+T 细胞促炎分化为 Th17 细胞。在沉默 tMSCs 中 TSP-1 的表达后，MEXsLPS 的促炎作用受到抑制。因此，这些发现揭示了 TSP-1 作为 MEXsLPS 促炎调节的主要因素。