Unexpected positive control of NFκB and miR-155 by DGKα and ζ ensures effector and memory CD8+ T cell differentiation.
Oncotarget
; 7(23): 33744-64, 2016 Jun 07.
Article
in En
| MEDLINE
| ID: mdl-27014906
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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
NF-kappa B
/
CD8-Positive T-Lymphocytes
/
Diacylglycerol Kinase
/
MicroRNAs
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Year:
2016
Type:
Article