▎ 摘　　要

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 alpha-galactosylceramide (alpha-GalCer), an iNKT cell agonist. We found that in vivo GO treatment substantially inhibited the capacity of alpha-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 gamma delta(T) cells. Such effects of GO on alpha-GalCer-induced inflammatory responses closely correlated with iNKT cell polarization towards TGF beta 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 alpha-GalCer-elicited responses, implying negative effects of TLR4 signaling on the anti-inflammatory properties of GO. By employing an alpha-GalCer-induced sepsis model, we further demonstrated that GO treatment significantly protected mice from alpha-GalCer-induced lethality. Taken together, we provide strong evidence that GO holds promise as an adjuvant to modulate iNKT cell responses for immunotherapy.