Graphene quantum dots induce tolerogenic properties in dendritic cells via induction of autophagy
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Janjetović, Kristina D.
Trajković, Vladimir S.
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Graphene quantum dots (GQD) are atom-thick nanodimensional carbon, very attractive for the application in theranostics due to their excellent physico-chemical and biological properties. However, their immunoregulatory properties are insufficiently investigated, especially for human 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 purified 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+CD25hiFoxp3hi regulatory T cells. After internalization in a dynamin-independent, cholesterol-dependent manner, GQD lowered th...e ROS generation and nuclear translocation of NF-B 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.
Извор:European Journal of Immunology, 2018, 48, Supplement 1, 180-181
- 15th International Symposium on Dendritic Cells (DC), Aachen, Germany, 10-14 June 2018
ISSN: 0014-2980 (print); 1521-4141 (electronic)