Unexpected positive control of NFκB and miR-155 by DGKα and ζ ensures effector and memory CD8+ T cell differentiation.

Published

Journal Article

Signals from the T-cell receptor (TCR) and γ-chain cytokine receptors play crucial roles in initiating activation and effector/memory differentiation of CD8 T-cells. We report here that simultaneous deletion of both diacylglycerol kinase (DGK) α and ζ (DKO) severely impaired expansion of CD8 effector T cells and formation of memory CD8 T-cells after Listeria monocytogenes infection. Moreover, ablation of both DGKα and ζ in preformed memory CD8 T-cells triggered death and impaired homeostatic proliferation of these cells. DKO CD8 T-cells were impaired in priming due to decreased expression of chemokine receptors and migration to the draining lymph nodes. Moreover, DKO CD8 T-cells were unexpectedly defective in NFκB-mediated miR-155 transcript, leading to excessive SOCS1 expression and impaired γ-chain cytokine signaling. Our data identified a DGK-NFκB-miR-155-SOCS1 axis that bridges TCR and γ-chain cytokine signaling for robust CD8 T-cell primary and memory responses to bacterial infection.

Full Text

Duke Authors

Cited Authors

  • Yang, J; Zhang, P; Krishna, S; Wang, J; Lin, X; Huang, H; Xie, D; Gorentla, B; Huang, R; Gao, J; Li, Q-J; Zhong, X-P

Published Date

  • June 7, 2016

Published In

Volume / Issue

  • 7 / 23

Start / End Page

  • 33744 - 33764

PubMed ID

  • 27014906

Pubmed Central ID

  • 27014906

Electronic International Standard Serial Number (EISSN)

  • 1949-2553

Digital Object Identifier (DOI)

  • 10.18632/oncotarget.8164

Language

  • eng

Conference Location

  • United States