Immunostimulatory Potential of Extracellular Vesicles Isolated from an Edible Plant, Petasites japonicus, via the Induction of Murine Dendritic Cell Maturation

Int J Mol Sci. 2021 Sep 30;22(19):10634. doi: 10.3390/ijms221910634.

Abstract

Extracellular vesicles (EVs) have recently been isolated from different plants. Plant-derived EVs have been proposed as potent therapeutics and drug-delivery nanoplatforms for delivering biomolecules, including proteins, RNAs, DNAs, and lipids. Herein, Petasites japonicus-derived EVs (PJ-EVs) were isolated through a series of centrifugation steps and characterized using dynamic light scattering and transmission electron microscopy. Immunomodulatory effects of PJ-EVs were assessed using dendritic cells (DCs). PJ-EVs exhibited a spherical morphology with an average size of 122.6 nm. They induced the maturation of DCs via an increase in the expression of surface molecules (CD80, CD86, MHC-I, and MHC-II), production of Th1-polarizing cytokines (TNF-α and IL-12p70), and antigen-presenting ability; however, they reduced the antigen-uptake ability. Furthermore, maturation of DCs induced by PJ-EVs was dependent on the activation and phosphorylation of MAPK and NF-κB signal pathways. Notably, PJ-EV-treated DCs strongly induced the proliferation and differentiation of naïve T cells toward Th1-type T cells and cytotoxic CD8+ T cells along with robust secretion of IFN-γ and IL-2. In conclusion, our study indicates that PJ-EVs can be potent immunostimulatory candidates with an ability of strongly inducing the maturation of DCs.

Keywords: Petasites japonicus; T cells; dendritic cells; extracellular vesicles; immunostimulatory.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / drug effects*
  • Cell Differentiation / immunology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cytokines / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Extracellular Vesicles / immunology*
  • Female
  • Lymphocyte Activation / drug effects
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Petasites / cytology*
  • Plants, Edible / cytology*
  • Th1 Cells / immunology

Substances

  • Adjuvants, Immunologic
  • Cytokines
  • NF-kappa B
  • Mitogen-Activated Protein Kinases