First Author | Zhu M | Year | 2018 |
Journal | J Immunol | Volume | 200 |
Issue | 6 | Pages | 2165-2173 |
PubMed ID | 29386256 | Mgi Jnum | J:259799 |
Mgi Id | MGI:6121673 | Doi | 10.4049/jimmunol.1701291 |
Citation | Zhu M, et al. (2018) Phospholipase D in TCR-Mediated Signaling and T Cell Activation. J Immunol 200(6):2165-2173 |
abstractText | 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 PKCtheta 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. |