Graphene quantum dots suppress proinflammatory T cell responses via autophagy-dependent induction of tolerogenic dendritic cells

Biomaterials. 2017 Nov;146:13-28. doi: 10.1016/j.biomaterials.2017.08.040. Epub 2017 Aug 29.

Abstract

Graphene quantum dots (GQD) are atom-thick nanodimensional carbon sheets with excellent physico-chemical and biological properties, making them attractive for application in theranostics. However, their immunoregulatory properties are insufficiently investigated, especially in human primary immune cells. We found that non-toxic doses of GQD inhibit the production of proinflammatory and T helper (Th)1 cytokines, and augment the production of anti-inflammatory and Th2 cytokines by human peripheral blood mononuclear cells. While unable to affect T cells directly, GQD impaired the differentiation and functions of monocyte-derived dendritic cells (DC), lowering their capacity to stimulate T cell proliferation, development of Th1 and Th17 cells, and T-cell mediated cytotoxicity. Additionally, GQD-treated DC potentiated Th2 polarization, and induced suppressive CD4+CD25highFoxp3+ regulatory T cells. After internalization in a dynamin-independent, cholesterol-dependent manner, GQD lowered the production of reactive oxygen species and nuclear translocation of NF-κB in DC. The activity of mammalian target of rapamycin (mTOR) was reduced by GQD, which correlated with the increase in transcription of autophagy genes and autophagic flux in DC. Genetic suppression of autophagy impaired the pro-tolerogenic effects of GQD on DC. Our results suggest that GQD-triggered autophagy promotes tolerogenic functions in monocyte-derived DC, which could be beneficial in inflammatory T-cell mediated pathologies, but also harmful in GQD-based anti-cancer therapy.

Keywords: Autophagy; Dendritic cells; Graphene quantum dots; Regulatory T cells; Tolerance.

MeSH terms

  • Autophagy / drug effects
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cytokines / metabolism
  • Dendritic Cells / cytology*
  • Dendritic Cells / drug effects*
  • Flow Cytometry
  • Graphite / chemistry*
  • Graphite / pharmacology*
  • Humans
  • Immunoblotting
  • Quantum Dots / chemistry*
  • Real-Time Polymerase Chain Reaction
  • T-Lymphocytes, Regulatory / drug effects

Substances

  • Cytokines
  • Graphite