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TBK-binding protein 1 regulates IL-15-induced autophagy and NKT cell survival
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TBK-binding protein 1 regulates IL-15-induced autophagy and NKT cell survival
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Journal Article
TBK-binding protein 1 regulates IL-15-induced autophagy and NKT cell survival
2018
Overview
The cytokine IL-15 mediates development and survival of immune cells, including natural killer T (NKT) cells, but the underlying mechanism of IL-15 function is incompletely understood. Here we show that IL-15 induces autophagy in NKT cells with a mechanism that involves a crucial signaling component, TBK-binding protein 1 (Tbkbp1). Tbkbp1 facilitates activation of the autophagy-initiating kinase Ulk1 through antagonizing the inhibitory action of mTORC1. This antagonization involves the recruitment of an mTORC1-opposing phosphatase to Ulk1. Tbkbp1 deficiency attenuates IL-15-stimulated NKT cell autophagy, and is associated with mitochondrial dysfunction, aberrant ROS production, defective Bcl2 expression and reduced NKT cell survival. Consequently, Tbkbp1-deficient mice have profound deficiency in NKT cells, especially IFN-γ-producing NKT1. We further show that Tbkbp1 regulates IL-15-stimulated autophagy and survival of NK cells. These findings suggest a mechanism of autophagy induction by IL-15, and establish Tbkbp1 as a regulator of NKT cell development and survival.
Interleukin-15 (IL-15) regulates the homeostasis of many immune cell types, including natural killer T (NKT) cells, but the underlying mechanism is not completely clear. Here the authors analyse
Tbkbp1
-deficient mice and show that IL-15 induces Tbkbp1-dependent autophagy to modulate NKT survival.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 96
/ 96/106
/ 96/109
/ 96/31
/ Adaptor Proteins, Signal Transducing - deficiency
/ Adaptor Proteins, Signal Transducing - genetics
/ Adaptor Proteins, Signal Transducing - immunology
/ Animals
/ Autophagy-Related Protein-1 Homolog - genetics
/ Autophagy-Related Protein-1 Homolog - immunology
/ Humanities and Social Sciences
/ Interferon-gamma - immunology
/ Mechanistic Target of Rapamycin Complex 1 - genetics
/ Mechanistic Target of Rapamycin Complex 1 - immunology
/ Mice
/ Natural Killer T-Cells - immunology
/ Natural Killer T-Cells - pathology
/ Proteins
/ Proto-Oncogene Proteins c-bcl-2 - genetics
/ Proto-Oncogene Proteins c-bcl-2 - immunology
/ Reactive Oxygen Species - immunology
/ Reactive Oxygen Species - metabolism
/ Science
/ Survival
