title: Phospholipase C{gamma}1 is essential for T cell development, activation, and tolerance.
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.
authors.affiliation: The Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Guoping
authors.initials: G
authors.lastname: Fu
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Chen
authors.forename: Mei
authors.initials: M
authors.lastname: Yu
authors.forename: Andy
authors.initials: A
authors.lastname: Podd
authors.forename: James
authors.initials: J
authors.lastname: Schuman
authors.forename: Yinghong
authors.initials: Y
authors.lastname: He
authors.forename: Lie
authors.initials: L
authors.lastname: Di
authors.forename: Maryam
authors.initials: M
authors.lastname: Yassai
authors.forename: Dipica
authors.initials: D
authors.lastname: Haribhai
authors.forename: Paula E
authors.initials: PE
authors.lastname: North
authors.forename: Jack
authors.initials: J
authors.lastname: Gorski
authors.forename: Calvin B
authors.initials: CB
authors.lastname: Williams
authors.forename: Demin
authors.initials: D
authors.lastname: Wang
authors.forename: Renren
authors.initials: R
authors.lastname: Wen
mesh_terms: 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
chemical_list: 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