Phospholipase C{gamma}1 is essential for T cell development, activation, and tolerance.
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.
Fu
Guoping
G
The Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53226, USA.
Chen
Yuhong
Y
Yu
Mei
M
Podd
Andy
A
Schuman
James
J
He
Yinghong
Y
Di
Lie
L
Yassai
Maryam
M
Haribhai
Dipica
D
North
Paula E
PE
Gorski
Jack
J
Williams
Calvin B
CB
Wang
Demin
D
Wen
Renren
R
D000818:Animals; D001327:Autoimmune Diseases / Q000201:enzymology / Q000276:immunology; D015551:Autoimmunity; D002454:Cell Differentiation; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000201:enzymology / Q000276:immunology; D008213:Lymphocyte Activation; D048670:MAP Kinase Kinase 4 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000276:immunology / Q000378:metabolism; D051966:Phospholipase C gamma / Q000172:deficiency / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000276:immunology
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D011948:Receptors, Antigen, T-Cell; D018808:Transcription Factor AP-1; D048670:MAP Kinase Kinase 4; D051966:Phospholipase C gamma