| First Author | Xie D | Year | 2020 |
| Journal | Eur J Immunol | Volume | 50 |
| Issue | 11 | Pages | 1729-1745 |
| PubMed ID | 32525220 | Mgi Jnum | J:298856 |
| Mgi Id | MGI:6473050 | Doi | 10.1002/eji.201948442 |
| Citation | Xie D, et al. (2020) Negative control of diacylglycerol kinase zeta-mediated inhibition of T cell receptor signaling by nuclear sequestration in mice. Eur J Immunol 50(11):1729-1745 |
| abstractText | Diacylglycerol kinases (DGKs) play important roles in restraining diacylglycerol (DAG)-mediated signaling. Within the DGK family, the zeta isoform appears to be the most important isoform in T cells for controlling their development and function. DGKzeta has been demonstrated to regulate T cell maturation, activation, anergy, effector/memory differentiation, defense against microbial infection, and antitumor immunity. Given its critical functions, DGKzeta function should be tightly regulated to ensure proper signal transduction; however, mechanisms that control DGKzeta function are still poorly understood. We report here that DGKzeta dynamically translocates from the cytosol into the nuclei in T cells after TCR stimulation. In mice, DGKzeta mutant defective in nuclear localization displayed enhanced ability to inhibit TCR-induced DAG-mediated signaling in primary T cells, maturation of conventional alphabetaT and iNKT cells, and activation of peripheral T cells compared with WT DGKzeta. Our study reveals for the first time nuclear sequestration of DGKzeta as a negative control mechanism to spatially restrain it from terminating DAG mediated signaling in T cells. Our data suggest that manipulation of DGKzeta nucleus-cytosol shuttling as a novel strategy to modulate DGKzeta activity and immune responses for treatment of autoimmune diseases and cancer. |
