Abstract
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.
Highlights
Mesenchymal stromal cells (MSCs) are adult, fibroblast-like multipotent cells that widely exist in a variety of body tissues
Stable TSP-1 knockdown cells for thymic mesenchymal stromal cells (tMSCs) were generated via transfection with TSP-1-specific short hairpin RNA (SHCLND-NM 003246.2-3029s21c1 for sh1, SHCLND-NM 003246.2-3071s21c1 for sh2, Sigma-Aldrich) lentivirus, and positively selected with ampicillin (10 μg/ml, Solarbio)
Human cells stimulation tMSCs were pretreated with LPS (1 μg/ml, Solarbio) or Poly (I:C) (50 μg/ml, Invivogen) in 24, 48 and 72 h, and the expression of TSP-1 was detect in tMSCs by quantitative real-time PCR and Western blot. tMSCs were infected with TSP-1 knockdown lentivirus for 72 h, and the expression of TSP-1 was detected in tMSCs
Summary
Mesenchymal stromal cells (MSCs) are adult, fibroblast-like multipotent cells that widely exist in a variety of body tissues. MSCs participate in immune regulation and tissue repair. At stages of illness, the low inflammation levels significantly reduce the therapeutic effect of MSCs and can promote the development of the disease [7]. When no inflammation arises or is in a low state, MSCs show reduced effectivity in GvHD treatment [8,9]. The therapeutic effect is weakened in experimental autoimmune encephalomyelitis when MSCs are transplanted during disease remission [10,11]. Based on these observations, MSCs can either promote or suppress immune responses.
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