Glycogen synthase kinase 3 (GSK-3) controls T-cell motility and interactions with antigen presenting cells

Author:

Taylor Alison,Rudd Christopher E.ORCID

Abstract

Abstract Objective The threonine/serine kinase glycogen synthase kinase 3 (GSK-3) targets multiple substrates in T-cells, regulating the expression of Tbet and PD-1 on T-cells. However, it has been unclear whether GSK-3 can affect the motility of T-cells and their interactions with antigen presenting cells. Results Here, we show that GSK-3 controls T-cell motility and interactions with other cells. Inhibition of GSK-3, using structurally distinct inhibitors, reduced T-cell motility in terms of distance and displacement. While SB415286 reduced the number of cell-cell contacts, the dwell times of cells that established contacts with other cells did not differ for T-cells treated with SB415286. Further, the increase in cytolytic T-cell (CTL) function in killing tumor targets was not affected by the inhibition of motility. This data shows 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.

Funder

Wellcome Trust

Publisher

Springer Science and Business Media LLC

Subject

General Biochemistry, Genetics and Molecular Biology,General Medicine

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