Phospholipase D in TCR-Mediated Signaling and T Cell Activation.

Published

Journal Article

Phospholipase D (PLD) is an enzyme that catalyzes the hydrolysis of phosphatidylcholine, the major phospholipid in the plasma membrane, to generate an important signaling lipid, phosphatidic acid. Phosphatidic acid is a second messenger that regulates vesicular trafficking, cytoskeletal reorganization, and cell signaling in immune cells and other cell types. Published studies, using pharmacological inhibitors or protein overexpression, indicate that PLD plays a positive role in TCR-mediated signaling and cell activation. In this study, we used mice deficient in PLD1, PLD2, or both to assess the function of these enzymes in T cells. Our data showed that PLD1 deficiency impaired TCR-mediated signaling, T cell expansion, and effector function during immune responses against Listeria monocytogenes; however, PLD2 deficiency had a minimal impact on T cells. Biochemical analysis indicated that PLD1 deficiency affected Akt and PKCθ activation. In addition, it impaired TCR downregulation and the secondary T cell response. Together, our results suggested that PLD1 plays an important role in T cell activation.

Full Text

Duke Authors

Cited Authors

  • Zhu, M; Foreman, DP; O'Brien, SA; Jin, Y; Zhang, W

Published Date

  • March 15, 2018

Published In

Volume / Issue

  • 200 / 6

Start / End Page

  • 2165 - 2173

PubMed ID

  • 29386256

Pubmed Central ID

  • 29386256

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1701291

Language

  • eng

Conference Location

  • United States