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Graphene oxide polarizes iNKT cells for production of TGFβ and attenuates inflammation in an iNKT cell-mediated sepsis model.

Sung Won Lee | Hyun Jung Park | Luc Van Kaer | Suklyun Hong | Seokmann Hong
Scientific reports | 2018

Graphene oxide (GO) modulates the functions of antigen-presenting cells including dendritic cells (DCs). Although carbon nanotubes affect expression of the MHC class I-like CD1d molecule, whether GO can influence immune responses of CD1d-dependent invariant natural killer T (iNKT) cells remains unclear. Here, we investigated the impact of GO on inflammatory responses mediated by α-galactosylceramide (α-GalCer), an iNKT cell agonist. We found that in vivo GO treatment substantially inhibited the capacity of α-GalCer to induce the iNKT cell-mediated trans-activation of and cytokine production by innate and innate-like cells, including DCs, macrophages, NK cells, and γδ T cells. Such effects of GO on α-GalCer-induced inflammatory responses closely correlated with iNKT cell polarization towards TGFβ production, which also explains the capacity of GO to expand regulatory T cells. Interestingly, the absence of TLR4, a receptor for GO, failed to downregulate, and instead partially enhanced the anti-inflammatory activity of GO against α-GalCer-elicited responses, implying negative effects of TLR4 signaling on the anti-inflammatory properties of GO. By employing an α-GalCer-induced sepsis model, we further demonstrated that GO treatment significantly protected mice from α-GalCer-induced lethality. Taken together, we provide strong evidence that GO holds promise as an adjuvant to modulate iNKT cell responses for immunotherapy.

Pubmed ID: 29973666

Research resources used in this publication

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Antibodies used in this publication

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Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK058404
  • Agency: National Research Foundation of Korea (NRF), International
    Id: NRF-2016R1A6A3A11936337
  • Agency: National Research Foundation of Korea (NRF), International
    Id: 2010-0020207
  • Agency: National Research Foundation of Korea (NRF), International
    Id: NRF-2016R1D1A1A09919293

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