PI3Kgamma (PI3Kγ) is essential for efficient induction of CXCR3 on activated T cells

The gamma isoform of PI3Kinase (PI3Kγ) controls leukocyte chemotaxis by participating in GPCR signaling, and by regulating cellular polarization. Here we show that PI3Kγ is required for efficient induction of CXC chemokine receptor 3 (CXCR3) on T cells upon activation. T cells from PI3Kγ−/−mice up-regulated CXCR3 less efficiently than wild-type controls both upon activation in vitro as well as during Leishmania mexicanainfection. Inhibition of PI3Kinases using wortmannin and LY294002 or blockade of PI3Kγ activity using a selective inhibitor or PI3Kγ siRNA suppressed induction of CXCR3 on T cells following activation. Levels of CXCR3 and T-bet mRNA were significantly lower in PI3Kγ inhibitor–treated T cells, indicating that PI3Kγ may control CXCR3 expression in part through induction of T-bet. These results reveal a novel role for PI3Kγ in the induction of CXCR3 on T cells and suggest that PI3Kγ may regulate leukocyte chemotaxis by controlling the expression of chemokine receptors.