We found that resveratrol enhances interferon (IFN)-y-induced tryptophanyl-tRNA-synthetase (TTS) expression in bone marrow- derived dendritic cells (BMDCs). Resveratrol-induced TTS expression is associated with glycogen synthase kinase-3B (GSK-3B) activity. In addition, we found that resveratrol regulates naive CD8+ T-cell polarization by modulating GSK-3B activity in IFN-Y-stimulated BMDCs, and that resveratol induces upregulation of TTS in CD8+ T-cells in the in vivo tumor environment. Taken together, resveratrol upregulates IFN-Y-induced TTS expression in a GSK-3B-dependent manner, and this TTS modulation is crucial for DC-mediated T-cell modulation. [BMB Reports 2015; 48(5): 283-288]