Submitted February 4, 2008
Accepted July 15, 2008
PI3Kgamma (PI3K
) is essential for efficient induction of CXCR3 on activated T cells
Joseph Barbi, Hannah E Cummings, Bao Lu, Steve Oghumu, Thomas Ruckle, Christian Rommel, William Lafuse, Caroline Whitacre, and Abhay R. Satoskar*
Microbiology, The Ohio State University, Columbus, OH, United States
Ina Sue Perlmutter Laboratory, Children's Hospital, Harvard Medical School, Boston, MA, United States
Cell Signaling, Merck Serono International S.A., Geneva, Switzerland
Intellikine Inc, La Jolla, CA, United States
MVIMG, The Ohio State University, Columbus, OH, United States
* Corresponding author; email: satoskar.2{at}osu.edu.
The gamma isoform of PI3Kinase (PI3K
) controls leukocyte chemotaxis by participating in GPCR signaling, and by regulating cellular polarization. Here we show that PI3K is required for efficient induction of CXC chemokine receptor 3 (CXCR3) on T cells upon activation. T cells from PI3K-/- mice up-regulated CXCR3 less efficiently than wild type controls both upon activation in vitro as well as during Leishmania mexicana infection. Inhibition of PI3Kinases using wortmanin and LY294002 or blockade of PI3K activity using a selective inhibitor or PI3K siRNA suppressed induction of CXCR3 on T cells following activation. Levels of CXCR3 and T-bet mRNA were significantly lower in PI3K inhibitor-treated T cells, indicating that PI3K may control CXCR3 expression in part through induction of T-bet. These results reveal a novel role for PI3K in the induction of CXCR3 on T-cells and suggest that PI3K may regulate leukocyte chemotaxis by controlling the expression of chemokine receptors.
