Regulation of T-cell activation and migration by the kinase TBK1 during neuroinflammation

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 and Shao-Cong Sun ()
Additional contact information
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
Jae-Hoon Chang: The University of Texas MD Anderson Cancer Center
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
Wei Cao: The University of Texas MD Anderson Cancer Center
Anna Zal: The University of Texas MD Anderson Cancer Center
Tomasz Zal: The University of Texas MD Anderson Cancer Center
Shao-Cong Sun: The University of Texas MD Anderson Cancer Center

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: 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.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms7074 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7074

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms7074

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().