| First Author | Lee SW | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 10081 |
| PubMed ID | 29973666 | Mgi Jnum | J:269092 |
| Mgi Id | MGI:6271368 | Doi | 10.1038/s41598-018-28396-9 |
| Citation | Lee SW, et al. (2018) Graphene oxide polarizes iNKT cells for production of TGFbeta and attenuates inflammation in an iNKT cell-mediated sepsis model. Sci Rep 8(1):10081 |
| abstractText | 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 gammadelta T cells. Such effects of GO on alpha-GalCer-induced inflammatory responses closely correlated with iNKT cell polarization towards TGFbeta 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. |
