Phospholipase Cγ1 is required for pre-TCR signal transduction and pre-T cell development. Eur J Immunol 2017 Jan;47(1):74-83
Date
10/21/2016Pubmed ID
27759161Pubmed Central ID
PMC5559087DOI
10.1002/eji.201646522Scopus ID
2-s2.0-84999652051 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
Pre-T cell receptor (TCR) signaling is required for pre-T cell survival, proliferation, and differentiation from the CD4 and CD8 double negative (DN) to the double positive (DP) stage. However, the pre-TCR signal transduction pathway is not fully understood and the signaling molecules involved have not been completely identified. Phospholipase Cγ (PLCγ) 1 is an important signaling molecule that generates two second messengers, diacylglycerol and inositol 1,4,5-trisphosphate, that are important to mediate PKC activation and intracellular Ca2+ flux in many signaling pathways. Previously, we have shown that PLCγ1 is important for TCR-mediated signaling, development and T-cell activation, but the role of PLCγ1 in pre-TCR signal transduction and pre-T cell development is not known. In this study, we demonstrated that PLCγ1 expression level in pre-T cells was comparable to that in mature T cells. Deletion of PLCγ1 prior to the pre-TCR signaling stage partially blocked the DN3 to DN4 transition and reduced thymic cellularity. We also demonstrated that deletion of PLCγ1 impaired pre-T cell proliferation without affecting cell survival. Further study showed that deficiency of PLCγ1 impaired pre-TCR mediated Ca2+ flux and Erk activation. Thus our studies demonstrate that PLCγ1 is important for pre-TCR mediated signal transduction and pre-T cell development.
Author List
Fu G, Yu M, Chen Y, Zheng Y, Zhu W, Newman DK, Wang D, Wen RAuthors
Debra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of WisconsinDebra K. Newman PhD Professor in the Pharmacology and Toxicology 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
MESH terms used to index this publication - Major topics in bold
AnimalsBiomarkers
Calcium
Cell Differentiation
Cell Proliferation
Cell Survival
Extracellular Signal-Regulated MAP Kinases
Gene Expression
Genotype
Lymphocyte Activation
Mice
Mice, Transgenic
Phospholipase C gamma
Phosphorylation
Precursor Cells, T-Lymphoid
Receptors, Antigen, T-Cell
Receptors, Antigen, T-Cell, alpha-beta
Signal Transduction
Thymocytes