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- Title
Negative control of diacylglycerol kinase ζ‐mediated inhibition of T cell receptor signaling by nuclear sequestration in mice.
- Authors
Xie, Danli; Zhang, Shimeng; Chen, Pengcheng; Deng, Wenhai; Pan, Yun; Xie, Jinhai; Wang, Jinli; Liao, Bryce; Sleasman, John W.; Zhong, Xiao‐Ping
- Abstract
Diacylglycerol kinases (DGKs) play important roles in restraining diacylglycerol (DAG)‐mediated signaling. Within the DGK family, the ζ isoform appears to be the most important isoform in T cells for controlling their development and function. DGKζ has been demonstrated to regulate T cell maturation, activation, anergy, effector/memory differentiation, defense against microbial infection, and antitumor immunity. Given its critical functions, DGKζ function should be tightly regulated to ensure proper signal transduction; however, mechanisms that control DGKζ function are still poorly understood. We report here that DGKζ dynamically translocates from the cytosol into the nuclei in T cells after TCR stimulation. In mice, DGKζ mutant defective in nuclear localization displayed enhanced ability to inhibit TCR‐induced DAG‐mediated signaling in primary T cells, maturation of conventional αβT and iNKT cells, and activation of peripheral T cells compared with WT DGKζ. Our study reveals for the first time nuclear sequestration of DGKζ as a negative control mechanism to spatially restrain it from terminating DAG mediated signaling in T cells. Our data suggest that manipulation of DGKζ nucleus‐cytosol shuttling as a novel strategy to modulate DGKζ activity and immune responses for treatment of autoimmune diseases and cancer.
- Subjects
T cell receptors; CELL communication; T cells; NUCLEAR receptors (Biochemistry); CELL nuclei; CELLULAR signal transduction
- Publication
European Journal of Immunology, 2020, Vol 50, Issue 11, p1729
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201948442