Author
Listed:
- Jiayi Yu
(The University of Texas MD Anderson Cancer Center)
- Xiaofei Zhou
(The University of Texas MD Anderson Cancer Center)
- Mikyoung Chang
(The University of Texas MD Anderson Cancer Center)
- Mako Nakaya
(The University of Texas MD Anderson Cancer Center
School of Medicine, University of Fukui)
- Jae-Hoon Chang
(The University of Texas MD Anderson Cancer Center
College of Pharmacy, Yeungnam University)
- Yichuan Xiao
(The University of Texas MD Anderson Cancer Center)
- J. William Lindsey
(University of Texas Health Science Center at Houston)
- Stephanie Dorta-Estremera
(The University of Texas MD Anderson Cancer Center
The University of Texas Graduate School of Biomedical Sciences at Houston)
- Wei Cao
(The University of Texas MD Anderson Cancer Center
The University of Texas Graduate School of Biomedical Sciences at Houston)
- Anna Zal
(The University of Texas MD Anderson Cancer Center)
- Tomasz Zal
(The University of Texas MD Anderson Cancer Center
The University of Texas Graduate School of Biomedical Sciences at Houston
Center for Inflammation and Cancer, The University of Texas MD Anderson Cancer Center)
- Shao-Cong Sun
(The University of Texas MD Anderson Cancer Center
The University of Texas Graduate School of Biomedical Sciences at Houston
Center for Inflammation and Cancer, The University of Texas MD Anderson Cancer Center)
Abstract
Development of an immune or autoimmune response involves T-cell activation in lymphoid organs and subsequent migration to peripheral tissues. Here we show that T-cell-specific ablation of the kinase TBK1 promotes T-cell activation but causes retention of effector T cells in the draining lymph node in a neuroinflammatory autoimmunity model, experimental autoimmune encephalomyelitis (EAE). At older ages, the T-cell-conditional TBK1-knockout mice also spontaneously accumulate T cells with activated phenotype. TBK1 controls the activation of AKT and its downstream kinase mTORC1 by a mechanism involving TBK1-stimulated AKT ubiquitination and degradation. The deregulated AKT-mTORC1 signalling in turn contributes to enhanced T-cell activation and impaired effector T-cell egress from draining lymph nodes. Treatment of mice with a small-molecule inhibitor of TBK1 inhibits EAE induction. These results suggest a role for TBK1 in regulating T-cell migration and establish TBK1 as a regulator of the AKT-mTORC1 signalling axis.
Suggested Citation
Jiayi Yu & Xiaofei Zhou & Mikyoung Chang & Mako Nakaya & Jae-Hoon Chang & Yichuan Xiao & J. William Lindsey & Stephanie Dorta-Estremera & Wei Cao & Anna Zal & Tomasz Zal & Shao-Cong Sun, 2015.
"Regulation of T-cell activation and migration by the kinase TBK1 during neuroinflammation,"
Nature Communications, Nature, vol. 6(1), pages 1-13, May.
Handle:
RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7074
DOI: 10.1038/ncomms7074
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