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Phospholipase Cγ1 is required for pre-TCR signal transduction and pre-T cell development. Eur J Immunol 2017 01;47(1):74-83

Date

10/21/2016

Pubmed ID

27759161

Pubmed Central ID

PMC5559087

DOI

10.1002/eji.201646522

Scopus ID

2-s2.0-84999652051   1 Citation

Abstract

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 Ca 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 Ca 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 R

Authors

Debra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of Wisconsin
Debra K. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Renren Wen PhD Associate Investigator in the Blood Research Institute department at BloodCenter of Wisconsin




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

Animals
Biomarkers
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
jenkins-FCD Prod-399 190a069c593fb5498b7fcd942f44b7bc9cdc7ea1