Phospholipase C-γ2 is a critical signaling mediator for murine NK cell activating receptors

Ilaria Tassi, Rachel Presti, Sung Jin Kim, Wayne M. Yokoyama, Susan Gilfillan, Marco Colonna

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Phospholipase C-γ (PLCγ) is a key regulator of intracellular Ca2+ mobilization. Two isoforms of PLCγ have been identified, PLCγ1 and PLCγ2. Previously, in vitro studies indicated that activating NK cell receptors signal through both isoforms. However, PLCγ2 deficiency alone was sufficient to induce a substantial impairment of NK cell-mediated cytotoxicity in vitro. Why PLCγ2 is more important than PLCγ1 for NK cell activation and whether PLCγ2 is also critical for NK cell development, secretion of IFN-γ, and clearance of viral infections in vivo is not known. In this study, we report that PLCγ2 is the predominant isoform expressed in murine NK cells. PLCγ2 deficiency did not affect NK cell numbers in bone marrow and spleen, but acquisition of Ly49 receptors by NK cells was partially impaired. PLCγ2-deficient NK cells exhibited a dramatic impairment of cytolytic function and IFN-γ production upon ligation of activating receptors, whereas they did secrete IFN-γ in response to cytokines. Consequently, mice lacking PLCγ2 controlled murine CMV infection substantially less effectively than did wild-type animals, and this defect was most evident in the spleen, where viral clearance mostly depends on NK cell lytic function. These results demonstrate that PLCγ2 is crucial for development of the NK cell receptor repertoire and signaling of activating NK cell receptors, mediating optimal NK cell function in vivo.

Original languageEnglish (US)
Pages (from-to)749-754
Number of pages6
JournalJournal of Immunology
Volume175
Issue number2
StatePublished - Jul 15 2005
Externally publishedYes

Fingerprint

Natural Killer Cell Receptors
Type C Phospholipases
Natural Killer Cells
Protein Isoforms
Spleen
Wild Animals
Virus Diseases
Ligation
Cell Count
Bone Marrow
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

Tassi, I., Presti, R., Kim, S. J., Yokoyama, W. M., Gilfillan, S., & Colonna, M. (2005). Phospholipase C-γ2 is a critical signaling mediator for murine NK cell activating receptors. Journal of Immunology, 175(2), 749-754.

Phospholipase C-γ2 is a critical signaling mediator for murine NK cell activating receptors. / Tassi, Ilaria; Presti, Rachel; Kim, Sung Jin; Yokoyama, Wayne M.; Gilfillan, Susan; Colonna, Marco.

In: Journal of Immunology, Vol. 175, No. 2, 15.07.2005, p. 749-754.

Research output: Contribution to journalArticle

Tassi, I, Presti, R, Kim, SJ, Yokoyama, WM, Gilfillan, S & Colonna, M 2005, 'Phospholipase C-γ2 is a critical signaling mediator for murine NK cell activating receptors', Journal of Immunology, vol. 175, no. 2, pp. 749-754.
Tassi I, Presti R, Kim SJ, Yokoyama WM, Gilfillan S, Colonna M. Phospholipase C-γ2 is a critical signaling mediator for murine NK cell activating receptors. Journal of Immunology. 2005 Jul 15;175(2):749-754.
Tassi, Ilaria ; Presti, Rachel ; Kim, Sung Jin ; Yokoyama, Wayne M. ; Gilfillan, Susan ; Colonna, Marco. / Phospholipase C-γ2 is a critical signaling mediator for murine NK cell activating receptors. In: Journal of Immunology. 2005 ; Vol. 175, No. 2. pp. 749-754.
@article{f59afc4524ee4ae9b37fe7073690ffa9,
title = "Phospholipase C-γ2 is a critical signaling mediator for murine NK cell activating receptors",
abstract = "Phospholipase C-γ (PLCγ) is a key regulator of intracellular Ca2+ mobilization. Two isoforms of PLCγ have been identified, PLCγ1 and PLCγ2. Previously, in vitro studies indicated that activating NK cell receptors signal through both isoforms. However, PLCγ2 deficiency alone was sufficient to induce a substantial impairment of NK cell-mediated cytotoxicity in vitro. Why PLCγ2 is more important than PLCγ1 for NK cell activation and whether PLCγ2 is also critical for NK cell development, secretion of IFN-γ, and clearance of viral infections in vivo is not known. In this study, we report that PLCγ2 is the predominant isoform expressed in murine NK cells. PLCγ2 deficiency did not affect NK cell numbers in bone marrow and spleen, but acquisition of Ly49 receptors by NK cells was partially impaired. PLCγ2-deficient NK cells exhibited a dramatic impairment of cytolytic function and IFN-γ production upon ligation of activating receptors, whereas they did secrete IFN-γ in response to cytokines. Consequently, mice lacking PLCγ2 controlled murine CMV infection substantially less effectively than did wild-type animals, and this defect was most evident in the spleen, where viral clearance mostly depends on NK cell lytic function. These results demonstrate that PLCγ2 is crucial for development of the NK cell receptor repertoire and signaling of activating NK cell receptors, mediating optimal NK cell function in vivo.",
author = "Ilaria Tassi and Rachel Presti and Kim, {Sung Jin} and Yokoyama, {Wayne M.} and Susan Gilfillan and Marco Colonna",
year = "2005",
month = "7",
day = "15",
language = "English (US)",
volume = "175",
pages = "749--754",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "2",

}

TY - JOUR

T1 - Phospholipase C-γ2 is a critical signaling mediator for murine NK cell activating receptors

AU - Tassi, Ilaria

AU - Presti, Rachel

AU - Kim, Sung Jin

AU - Yokoyama, Wayne M.

AU - Gilfillan, Susan

AU - Colonna, Marco

PY - 2005/7/15

Y1 - 2005/7/15

N2 - Phospholipase C-γ (PLCγ) is a key regulator of intracellular Ca2+ mobilization. Two isoforms of PLCγ have been identified, PLCγ1 and PLCγ2. Previously, in vitro studies indicated that activating NK cell receptors signal through both isoforms. However, PLCγ2 deficiency alone was sufficient to induce a substantial impairment of NK cell-mediated cytotoxicity in vitro. Why PLCγ2 is more important than PLCγ1 for NK cell activation and whether PLCγ2 is also critical for NK cell development, secretion of IFN-γ, and clearance of viral infections in vivo is not known. In this study, we report that PLCγ2 is the predominant isoform expressed in murine NK cells. PLCγ2 deficiency did not affect NK cell numbers in bone marrow and spleen, but acquisition of Ly49 receptors by NK cells was partially impaired. PLCγ2-deficient NK cells exhibited a dramatic impairment of cytolytic function and IFN-γ production upon ligation of activating receptors, whereas they did secrete IFN-γ in response to cytokines. Consequently, mice lacking PLCγ2 controlled murine CMV infection substantially less effectively than did wild-type animals, and this defect was most evident in the spleen, where viral clearance mostly depends on NK cell lytic function. These results demonstrate that PLCγ2 is crucial for development of the NK cell receptor repertoire and signaling of activating NK cell receptors, mediating optimal NK cell function in vivo.

AB - Phospholipase C-γ (PLCγ) is a key regulator of intracellular Ca2+ mobilization. Two isoforms of PLCγ have been identified, PLCγ1 and PLCγ2. Previously, in vitro studies indicated that activating NK cell receptors signal through both isoforms. However, PLCγ2 deficiency alone was sufficient to induce a substantial impairment of NK cell-mediated cytotoxicity in vitro. Why PLCγ2 is more important than PLCγ1 for NK cell activation and whether PLCγ2 is also critical for NK cell development, secretion of IFN-γ, and clearance of viral infections in vivo is not known. In this study, we report that PLCγ2 is the predominant isoform expressed in murine NK cells. PLCγ2 deficiency did not affect NK cell numbers in bone marrow and spleen, but acquisition of Ly49 receptors by NK cells was partially impaired. PLCγ2-deficient NK cells exhibited a dramatic impairment of cytolytic function and IFN-γ production upon ligation of activating receptors, whereas they did secrete IFN-γ in response to cytokines. Consequently, mice lacking PLCγ2 controlled murine CMV infection substantially less effectively than did wild-type animals, and this defect was most evident in the spleen, where viral clearance mostly depends on NK cell lytic function. These results demonstrate that PLCγ2 is crucial for development of the NK cell receptor repertoire and signaling of activating NK cell receptors, mediating optimal NK cell function in vivo.

UR - http://www.scopus.com/inward/record.url?scp=23244455179&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23244455179&partnerID=8YFLogxK

M3 - Article

C2 - 16002670

AN - SCOPUS:23244455179

VL - 175

SP - 749

EP - 754

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 2

ER -