Exosomes derived from LPS-stimulated human thymic mesenchymal stromal cells enhance inflammation via thrombospondin-1

Inflammatory response mediated by immune cells is either directly or indirectly reg-ulated 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 originat-ing from tMSCs (MEXs). Notably, exosomes derived from LPS-pretreated tMSCs (MEXs(LPS)) promoted the polarization of macrophages to M1-like phenotype and IL-6, TNF-alpha secre-tion 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 MEXs(LPS) were suppressed. Therefore, these findings uncovered TSP-1 as the principal factor in MEXs(LPS) pro-inflammatory regulation.