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

Title
Regulation of T-cell activation and migration by the kinase TBK1 during neuroinflammation
Author(s)
장재훈Jiayi Yu[Jiayi Yu]Xiaofei Zhou[Xiaofei Zhou]Mikyoung Chang[Mikyoung Chang]Mako Nakaya[Mako Nakaya]Yichuan Xiao[Yichuan Xiao]William Lindsey[William Lindsey]Stephanie Dorta-Estremera[Stephanie Dorta-Estremera]Wei Cao[Wei Cao]Anna Zal[Anna Zal]Tomaz Zal[Tomaz Zal]Shao-Cong Sun[Shao-Cong Sun]
Keywords
NF-KAPPA-B; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; IKK-EPSILON; L-SELECTIN; PHOSPHATIDYLINOSITOL 3-KINASE; ANTIVIRAL RESPONSE; VIRAL-INFECTION; RECEPTOR; FOXO1
Issue Date
201501
Publisher
NATURE PUBLISHING GROUP
Citation
NATURE COMMUNICATIONS, v.6
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.
URI
http://hdl.handle.net/YU.REPOSITORY/33681http://dx.doi.org/10.1038/ncomms7074
ISSN
2041-1723
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약학대학 > 약학부 > Articles
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