Piceatannol inhibits effector T cell functions by suppressing TcR signaling

Piceatannol, a metabolite of resveratrol found in red wine and grapes, displays a wide spectrum of biological activity. Although the anti-oxidant, anti-inflammatory, and anti-tumorigenesis activity of piceatannol has been extensively studied, its role in the adaptive immune response has received less attention. Here we investigated the role of piceatannol, a well-known Syk inhibitor, in T cell activation, proliferation, and differentiation using isolated murine splenic T cells from C57BL/6 mice. Piceatannol treatment inhibited surface expression of CD4 and CD8 T cell activation markers CD25 and CD69, reduced production of cytokines IFNγ, IL-2, and IL-17, and suppressed proliferation of activated T cells. Moreover, piceatannol treatment significantly inhibited differentiation of CD4⁺CD25^-CD62L⁺ naïve CD4 T cells into Th1, Th2, and Th17 cells, presumably due to inhibition of TcR signaling through p-Erk, p-Akt, and p-p38. Piceatannol appears to be a useful nutritional or pharmacological biomolecule that regulates effector T cell functions such as cytokine production, differentiation, and proliferation.