PI3Kgamma (PI3Kgamma) is essential for efficient induction of CXCR3 on activated T cells.
The gamma isoform of PI3Kinase (PI3Kgamma) controls leukocyte chemotaxis by participating in GPCR signaling, and by regulating cellular polarization. Here we show that PI3Kgamma is required for efficient induction of CXC chemokine receptor 3 (CXCR3) on T cells upon activation. T cells from PI3Kgamma(-/-) 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 wortmannin and LY294002 or blockade of PI3Kgamma activity using a selective inhibitor or PI3Kgamma siRNA suppressed induction of CXCR3 on T cells following activation. Levels of CXCR3 and T-bet mRNA were significantly lower in PI3Kgamma inhibitor-treated T cells, indicating that PI3Kgamma may control CXCR3 expression in part through induction of T-bet. These results reveal a novel role for PI3Kgamma in the induction of CXCR3 on T cells and suggest that PI3Kgamma may regulate leukocyte chemotaxis by controlling the expression of chemokine receptors.
Barbi
Joseph
J
Department of Microbiology, The Ohio State University, Columbus, USA.
Cummings
Hannah E
HE
Lu
Bao
B
Oghumu
Steve
S
Rückle
Thomas
T
Rommel
Christian
C
Lafuse
William
W
Whitacre
Caroline C
CC
Satoskar
Abhay R
AR
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002633:Chemotaxis; D002867:Chromones / Q000494:pharmacology; D058544:Class Ib Phosphatidylinositol 3-Kinase; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D007896:Leishmaniasis / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000469:parasitology; D015854:Up-Regulation; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; C515188:Cxcr3 protein, mouse; D007527:Isoenzymes; D009025:Morpholines; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D054367:Receptors, CXCR3; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D058544:Class Ib Phosphatidylinositol 3-Kinase; C546764:Pik3cg protein, mouse; D000077191:Wortmannin