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Differential and nonredundant roles of phospholipase Cgamma2 and phospholipase Cgamma1 in the terminal maturation of NK cells. J Immunol 2006 Oct 15;177(8):5365-76

Date

10/04/2006

Pubmed ID

17015722

DOI

10.4049/jimmunol.177.8.5365

Scopus ID

2-s2.0-33749524546   38 Citations

Abstract

NK cells play a central role in mediating innate immune responses. Activation of NK cells results in cytotoxicity, cytokine, and chemokine secretions. In this study, we show that in mice with targeted deletion of phospholipase Cgamma (PLCgamma)2, one of the key signal transducers, there are profound effects on the development and terminal maturation of NK cells. Lack of PLCgamma2 significantly impaired the ability of lineage-committed NK precursor cells to acquire subset-specific Ly49 receptors and thereby terminal maturation of NK cells. Overexpression of isozyme, PLCgamma1, in PLCgamma2-deficient NK cells resulted in the successful Ly49 acquisition and terminal maturation of the NK cells; however, it could only partially rescue NKG2D-mediated cytotoxicity with no cytokine production. Furthermore, PLCgamma2-deficient NK cells failed to mediate antitumor cytotoxicity and inflammatory cytokine production, displaying a generalized hyporesponsiveness. Our results strongly demonstrate that PLCgamma1 and PLCgamma2 play nonredundant and obligatory roles in NK cell ontogeny and in its effector functions.

Author List

Regunathan J, Chen Y, Kutlesa S, Dai X, Bai L, Wen R, Wang D, Malarkannan S

Authors

Subramaniam Malarkannan PhD Professor in the Medicine department at Medical College of Wisconsin
Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Renren Wen PhD Associate Investigator in the Blood Research Institute department at BloodCenter of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antigens, Ly
Cell Differentiation
Cell Lineage
Cytokines
Cytotoxicity, Immunologic
Killer Cells, Natural
Lectins, C-Type
Mice
Mice, Knockout
NK Cell Lectin-Like Receptor Subfamily K
Phospholipase C gamma
Receptors, Immunologic
Receptors, NK Cell Lectin-Like
Receptors, Natural Killer Cell
Signal Transduction
jenkins-FCD Prod-469 c3fc8ab87196149f9b23743c01b947d47e7319e5