The immunostimulatory role of Kupffer cells in various inflammatory liver diseases is still not fully understood. In this study, phenotypic and functional aspects of Kupffer cells from healthy C57BL/6 mice were analyzed and compared with those of splenic and peritoneal macrophages to generate a blueprint of the cells under steady-state conditions. In the mouse liver, only one population of Kupffer cells was identified as F4/ 80highCD11blow cells. We observed that freshy isolated Kupffer cells are endocytic and show a relatively high basal ROS content. Interestingly, despite expression of TLR mRNA on Kupffer cells, ligation of TLR4, TLR7/8, and TLR9 resulted in a weak induction of IL-10, low or undetectable levels of IL-12p40 and TNF, and up-regulation of CD40 on the surface. Kupffer cells and splenic macrophages show functional similarities, in comparison with peritoneal macrophages, as reflected by comparable levels of TLR4, TLR7/8, and TLR9 mRNA and low or undetectable levels of TNF and IL-12p40 produced upon TLR ligation. The unique, functional characteristics of Kupffer cells, demonstrated in this study, suggest that Kupffer cells under steady-state conditions are specialized as phagocytes to clear and degrade particulates and only play a limited immunoregulatory role via the release of soluble mediators.

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Keywords Endocytosis, IL-10, Immunoregulation, Liver
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Journal Journal of Leukocyte Biology
Movita, D, Kreefft, K, Biesta, P.J, van Oudenaren, A, Leenen, P.J, Janssen, H.L.A, & Boonstra, P.A. (2012). Kupffer cells express a unique combination of phenotypic and functional characteristics compared with splenic and peritoneal macrophages. Journal of Leukocyte Biology, 92(4), 723–733. doi:10.1189/jlb.1111566