Toll-like receptor 2/7 activation enhances the metabolism and functions of CD8+ T and B cells

Li, Qian GND

In our present study, we first examined whether TLR7 activation on CD8+ T cells can elevate the functionality of CD8+ T cells in the presence of αCD3 in vitro. We found that the enhanced functionality of CD8+ T cells relies on a MyD88 dependent manner, since the TLR2-MyD88 axis is believed to interact with the mTOR signaling pathway. We also found activated mTOR signaling in TLR7 costimulated CD8+ T cells. However, blocking mTOR signaling with inhibitors Rapamycin and Akti-1/2 can significantly reduce the enhanced function of CD8+ T cells. Not only the enhanced functionality of CD8+ T cells was affected by mTOR pathway blocking but also the enhanced glycolysis of CD8+ T cells. Glycolysis is further verified as essential for the regulation of CD8+ T cells by R848 blocking experiments. Besides the mTOR pathway, the downstream transcription factor IRF4 also participates in upregulating the glycolysis and functionality of TLR7-stimulated CD8+ T cells. TLR activation can be induced by different TLR agonists such as the TLR2 ligand P3C. P3C can also induce functional and metabolic alterations, especially glycolysis, in the same way as R848 in CD8+ T cells. The functional and metabolic alterations induced by TLR2/7 agonists in T cells can also be found in B cells. In summary, we observed the effects including the metabolic and functional alterations on TLR2/7 activated-CD8+ T and B cells. Our data provide a new possibility to manipulate immune functions by metabolic pathways in immune cells.

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Li, Q., 2020. Toll-like receptor 2/7 activation enhances the metabolism and functions of CD8+ T and B cells. https://doi.org/10.17185/duepublico/71754
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