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• W2788398088 abstract "Abstract Hepatic APCs play a critical role in promoting immune tolerance in the liver. Recently, we have demonstrated that TLR2 stimulation on liver sinusoidal endothelial cells reverted their suppressive properties to induce T cell immunity. However, there is a paucity of information about how TLR2 stimulation modulates the immunological function of other hepatic APCs. In the current study, we investigated whether TLR2 stimulation influences the function of intrahepatic myeloid-derived cells (iMDCs) and elucidated the mechanisms involved in iMDC-induced T cell immunity. We could show that iMDCs from C57BL/6 mice can potently suppress T cell activation in a cell contact–independent manner. Ag presentation by iMDCs leads to naive CD8 T cell tolerance. To our surprise, instead of inducing cell functional maturation, TLR2 ligand palmitoyl-3-cysteine-serine-lysine-4 (P3C) stimulation further strengthens the suppressive and tolerogenic properties of iMDCs. After P3C administration, the population of Kupffer cells (KCs) of iMDCs dramatically increased. Mechanism analysis shows that KCs are essential for the enhanced inhibition of T cell activation by P3C-stimulated iMDCs. The iMDC-mediated CD8 T cell inhibition was mediated by soluble mediators, one of which was IL-10 secreted by KCs after P3C stimulation. IL-10 blockade could partially abolish iMDC-mediated T cell inhibition. Moreover, hepatitis B virus particle stimulation on iMDCs could also induce IL-10 production by the cells in a TLR2-dependent way. Our results have implications for our understanding of liver-specific tolerance and for the development of strategies to overcome T cell tolerance in situations such as chronic viral liver infections." @default.
• W2788398088 created "2018-03-06" @default.
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• W2788398088 date "2018-04-01" @default.
• W2788398088 modified "2023-09-26" @default.
• W2788398088 title "TLR2 Stimulation Strengthens Intrahepatic Myeloid-Derived Cell-Mediated T Cell Tolerance through Inducing Kupffer Cell Expansion and IL-10 Production" @default.
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• W2788398088 doi "https://doi.org/10.4049/jimmunol.1700540" @default.
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