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

Li, Qian; Yan, Yan; Liu, Jia; Huang, Xuan; Zhang, Xiaoyong; Kirschning, Carsten GND; Xu, Haifeng C; Lang, Philipp A.; Dittmer, Ulf LSF; Zhang, Ejuan; Lu, Mengji GND

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 αCD3 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.

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Li, Qian / Yan, Yan / Liu, Jia / et al: Toll-Like Receptor 7 Activation Enhances CD8+ T Cell Effector Functions by Promoting Cellular Glycolysis.. 2019.

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