Abstract
Objective: The threonine/serine kinase glycogen synthase kinase 3 (GSK-3) targets multiple substrates in T-cells and regulates the expression of Tbet and PD-1. However, it has been unclear whether GSK-3 has any effect on T-cell motility or their interactions with antigen presenting cells.
Results: Here, we show that GSK-3 controls T-cell motilityand interactions with other cells. Inhibition of GSK-3, using structurally distinct inhibitors, reduced T-cell motility in terms of speed and distance travelled. Furthermore, SB415286 reduced the number of cell to cell contacts, however the duration of these established contacts with other cells did not differ in the presence of SB415286. This inhibition of motility did not affect the ability of GSK-3 inhibitors to enhance cytolytic T-cell (CTL) function in killing tumor targets. These data show that the inhibition of GSK-3 has differential effects on T-cell motility and CTL function where the negative effects on cell-cell interactions is overridden by the increased cytolytic potential of CTLs.
Glycogen Synthase Kinase-3 (GSK-3) Regulation of Inhibitory Coreceptor Expression in T-cell Immunity
