Oncotarget

Research Papers: Immunology:

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

Jialong Yang, Ping Zhang, Sruti Krishna, Jinli Wang, Xingguang Lin, Hongxiang Huang, Danli Xie, Balachandra Gorentla, Rick Huang, Jimin Gao, Qi-Jing Li and Xiao-Ping Zhong _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2016; 7:33744-33764. https://doi.org/10.18632/oncotarget.8164

Metrics: PDF 1126 views  |   HTML 1580 views  |   ?  


Abstract

Jialong Yang1, Ping Zhang1, Sruti Krishna1, Jinli Wang2, Xingguang Lin2, Hongxiang Huang1,3, Danli Xie1,2, Balachandra Gorentla1, Rick Huang1, Jimin Gao2, Qi-Jing Li4, and Xiao-Ping Zhong1,4

1 Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC, USA

2 School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China

3 Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China

4 Department of Immunology, Duke University Medical Center, Durham, NC, USA

Correspondence to:

Xiao-Ping Zhong, email:

Keywords: DGK, miR-155, NFκB, CD8 T cell, Listeria monocytogenes, Immunology and Microbiology Section, Immune response, Immunity

Received: January 11, 2016 Accepted: March 04, 2016 Published: March 17, 2016

Abstract

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 8164