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

Biosci Rep. 2021 Oct 29;41(10):BSR20203573. doi: 10.1042/BSR20203573.

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.

Keywords: Thymic mesenchymal stem cells; exosome; inflammation; thrombospondin-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Cytokines / metabolism
  • Exosomes / drug effects*
  • Exosomes / genetics
  • Exosomes / immunology
  • Exosomes / metabolism
  • Humans
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Inflammation Mediators / metabolism*
  • Lipopolysaccharides / pharmacology*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / immunology
  • Mesenchymal Stem Cells / metabolism
  • Phenotype
  • THP-1 Cells
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th17 Cells / immunology
  • Th17 Cells / metabolism
  • Thrombospondin 1 / genetics
  • Thrombospondin 1 / metabolism*
  • Thymus Gland / drug effects*
  • Thymus Gland / immunology
  • Thymus Gland / metabolism
  • Up-Regulation

Substances

  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • Thrombospondin 1
  • thrombospondin-1, human