The p110 delta of PI3K plays a critical role in NK cell terminal maturation and cytokine/chemokine generation. J Exp Med 2008 Sep 29;205(10):2419-35
Date
09/24/2008Pubmed ID
18809712Pubmed Central ID
PMC2556795DOI
10.1084/jem.20072327Scopus ID
2-s2.0-53349143413 (requires institutional sign-in at Scopus site) 89 CitationsAbstract
Phosphatidylinositol 3-kinases (PI3Ks) play a critical role in regulating B cell receptor- and T cell receptor-mediated signaling. However, their role in natural killer (NK) cell development and functions is not well understood. Using mice expressing p110 delta(D910A), a catalytically inactive p110 delta, we show that these mice had reduced NK cellularity, defective Ly49C and Ly49I NK subset maturation, and decreased CD27(High) NK numbers. p110 delta inactivation marginally impaired NK-mediated cytotoxicity against tumor cells in vitro and in vivo. However, NKG2D, Ly49D, and NK1.1 receptor-mediated cytokine and chemokine generation by NK cells was severely affected in these mice. Further, p110 delta(D910A/D910A) NK cell-mediated antiviral responses through natural cytotoxicity receptor 1 were reduced. Analysis of signaling events demonstrates that p110 delta(D910A/D910A) NK cells had a reduced c-Jun N-terminal kinase 1/2 phosphorylation in response to NKG2D-mediated activation. These results reveal a previously unrecognized role of PI3K-p110 delta in NK cell development and effector functions.
Author List
Guo H, Samarakoon A, Vanhaesebroeck B, Malarkannan SAuthor
Subramaniam Malarkannan PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntigens, Ly
Cell Line
Cell Proliferation
Chemokines
Class I Phosphatidylinositol 3-Kinases
Cytokines
Humans
Influenza A virus
Interferon-gamma
Killer Cells, Natural
Lectins, C-Type
Lymphocyte Subsets
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase 8
Mitogen-Activated Protein Kinase 9
NK Cell Lectin-Like Receptor Subfamily A
Phenotype
Phosphatidylinositol 3-Kinases
Protein Subunits
Receptors, NK Cell Lectin-Like
Signal Transduction
