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

被引：27

作者：

Barbi, Joseph ^{[1
]}

Cummings, Hannah E. ^{[1
]}

Lu, Bao ^{[2
]}

Oghumu, Steve ^{[1
]}

Rueckle, Thomas ^{[3
]}

Rommel, Christian ^{[4
]}

Lafuse, William ^{[5
]}

Whitacre, Caroline C. ^{[5
]}

Satoskar, Abhay R. ^{[1
]}

机构：

[1] Ohio State Univ, Dept Microbiol, Columbus, OH 43221 USA

[2] Harvard Univ, Sch Med, Childrens Hosp, Ina Sue Perlmutter Lab, Boston, MA USA

[3] Merck Serono Int SA, Geneva, Switzerland

[4] Intellikine, La Jolla, CA USA

[5] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA

来源：

BLOOD | 2008年 / 112卷 / 08期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1182/blood-2008-02-135715

中图分类号：

R5 [内科学];

学科分类号：

1002 [临床医学]; 100201 [内科学];

摘要：

The gamma isoform of PI3Kinase (PI3K gamma) controls leukocyte chemotaxis by participating in GPCR signaling, and by regulating cellular polarization. Here we show that PI3K gamma is required for efficient induction of CXC chemokine receptor 3 (CXCR3) on T cells upon activation. T cells from PI3K gamma(-/-) 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 PI3K gamma activity using a selective inhibitor or PI3K gamma siRNA suppressed induction of CXCR3 on T cells following activation. Levels of CXCR3 and T-bet mRNA were significantly lower in PI3K gamma inhibitor-treated T cells, indicating that PI3K gamma may control CXCR3 expression in part through induction of T-bet. These results reveal a novel role for PI3K gamma in the induction of CXCR3 on T cells and suggest that PI3K gamma may regulate leukocyte chemotaxis by controlling the expression of chemokine receptors.

引用

收藏

页码：3048 / 3051

页数：4

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