PI3Kgamma (PI3K{gamma}) 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 C. Whitacre; Abhay R. Satoskar

doi:10.1182/blood-2008-02-135715

PI3Kgamma (PI3K{gamma}) 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 C. Whitacre, Abhay R. Satoskar

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

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 mexicana infection. 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 inhibitortreated 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.

Original language	English (US)
Pages (from-to)	3048-3051
Number of pages	4
Journal	Blood
Volume	112
Issue number	8
DOIs	https://doi.org/10.1182/blood-2008-02-135715
State	Published - Oct 15 2008
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Immunology
Hematology
Cell Biology

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title = "PI3Kgamma (PI3K{gamma}) is essential for efficient induction of CXCR3 on activated T cells",

abstract = "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 mexicana infection. 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 inhibitortreated 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.",

author = "Joseph Barbi and Cummings, {Hannah E.} and Bao Lu and Steve Oghumu and Thomas Ruckle and Christian Rommel and William Lafuse and Whitacre, {Caroline C.} and Satoskar, {Abhay R.}",

year = "2008",

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doi = "10.1182/blood-2008-02-135715",

language = "English (US)",

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journal = "Blood",

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T1 - PI3Kgamma (PI3K{gamma}) is essential for efficient induction of CXCR3 on activated T cells

AU - Barbi, Joseph

AU - Cummings, Hannah E.

AU - Lu, Bao

AU - Oghumu, Steve

AU - Ruckle, Thomas

AU - Rommel, Christian

AU - Lafuse, William

AU - Whitacre, Caroline C.

AU - Satoskar, Abhay R.

PY - 2008/10/15

Y1 - 2008/10/15

N2 - 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 mexicana infection. 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 inhibitortreated 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.

AB - 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 mexicana infection. 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 inhibitortreated 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.

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PI3Kgamma (PI3K{gamma}) is essential for efficient induction of CXCR3 on activated T cells

Abstract

ASJC Scopus subject areas

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