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

Lee SW, Park HJ, Van Kaer L, Hong S, Hong S
Sci Rep. 2018 8 (1): 10081

PMID: 29973666 · PMCID: PMC6031608 · DOI:10.1038/s41598-018-28396-9

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.

MeSH Terms (17)

Animals Antigens, CD1d Cell Polarity Dendritic Cells Disease Models, Animal Galactosylceramides Graphite Humans Inflammation Intraepithelial Lymphocytes Lymphocyte Activation Mice Nanotubes, Carbon Natural Killer T-Cells Sepsis Toll-Like Receptor 4 Transforming Growth Factor beta

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