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Toll-Like Receptor 7 Activation Enhances CD8+ T Cell Effector Functions by Promoting Cellular Glycolysis.


ABSTRACT: The activation of TLR7 signaling in T cells accelerates antigen-specific responses. Such responses play an essential role in eliminating viral infections and can be anti-tumorigenic. However, the underlying mechanisms of how TLR7 can promote the optimal function of CD8+ T cells remain unclear. To investigate how TLR signaling directly contributes to CD8+ T cell functions, we examine the activation of cellular TLR7-related pathways and functional and metabolic alterations in TLR7-stimulated T cells during T cell receptor (TCR) signaling. In the present study, we investigated the activation of CD8+ T cells in response to direct stimulation by TLR7 ligands. TLR7 stimulation could promote the effector functions of purified CD8+ T cells in vitro. The TLR7-induced activation of CD8+ T cells occurs if CD8+ T cells were primed by ?CD3 activation and increasingly expressed TLR7. MyD88 and AKT-mTOR signaling plays a critical role in TLR7-induced T cell activation. In addition to the upregulation of immune-related genes, metabolic alterations in CD8+ T cells, including the upregulation of glucose uptake and glycolysis, occurred by TLR7 stimulation. Glycolysis was found to be regulated by the AKT-mTOR pathway and a downstream transcription factor IRF4. Blocking glycolysis by either direct glucose deprivation or modulating the mTOR pathway and IRF4 expression was found to impair T cell activation and functions. Taken together, the activation of TLR7 signaling promotes the effector functions of CD8+ T cells by enhancing cellular glycolysis.

SUBMITTER: Li Q 

PROVIDER: S-EPMC6751247 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Toll-Like Receptor 7 Activation Enhances CD8+ T Cell Effector Functions by Promoting Cellular Glycolysis.

Li Qian Q   Yan Yan Y   Liu Jia J   Huang Xuan X   Zhang Xiaoyong X   Kirschning Carsten C   Xu Haifeng C HC   Lang Philipp A PA   Dittmer Ulf U   Zhang Ejuan E   Lu Mengji M  

Frontiers in immunology 20190912


The activation of TLR7 signaling in T cells accelerates antigen-specific responses. Such responses play an essential role in eliminating viral infections and can be anti-tumorigenic. However, the underlying mechanisms of how TLR7 can promote the optimal function of CD8+ T cells remain unclear. To investigate how TLR signaling directly contributes to CD8+ T cell functions, we examine the activation of cellular TLR7-related pathways and functional and metabolic alterations in TLR7-stimulated T cel  ...[more]

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