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Phospholipase C{gamma}1 is essential for T cell development, activation, and tolerance. J Exp Med 2010 Feb 15;207(2):309-18

Date

02/04/2010

Pubmed ID

20123962

Pubmed Central ID

PMC2822604

DOI

10.1084/jem.20090880

Scopus ID

2-s2.0-77149154686 (requires institutional sign-in at Scopus site)   104 Citations

Abstract

Phospholipase Cgamma1 (PLCgamma1) is an important signaling effector of T cell receptor (TCR). To investigate the role of PLCgamma1 in T cell biology, we generated and examined mice with T cell-specific deletion of PLCgamma1. We demonstrate that PLCgamma1 deficiency affects positive and negative selection, significantly reduces single-positive thymocytes and peripheral T cells, and impairs TCR-induced proliferation and cytokine production, and the activation of ERK, JNK, AP-1, NFAT, and NF-kappaB. Importantly, PLCgamma1 deficiency impairs the development and function of FoxP3(+) regulatory T cells, causing inflammatory/autoimmune symptoms. Therefore, PLCgamma1 is essential for T cell development, activation, and tolerance.

Author List

Fu G, Chen Y, Yu M, Podd A, Schuman J, He Y, Di L, Yassai M, Haribhai D, North PE, Gorski J, Williams CB, Wang D, Wen R

Authors

Paula E. North MD, PhD Professor in the Pathology department at Medical College of Wisconsin
Demin Wang PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Renren Wen PhD Adjunct Associate Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Calvin B. Williams MD, PhD Chief, Professor in the Pediatrics department at Medical College of Wisconsin




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

Animals
Autoimmune Diseases
Autoimmunity
Cell Differentiation
Forkhead Transcription Factors
Inflammation
Lymphocyte Activation
MAP Kinase Kinase 4
Mice
Mice, Transgenic
NF-kappa B
NFATC Transcription Factors
Phospholipase C gamma
Receptors, Antigen, T-Cell
T-Lymphocyte Subsets
T-Lymphocytes
Transcription Factor AP-1