CD11c+ hepatic dendritic cells induce strong innate immune response with reduced capacity to activate allogeneic T cells (128.14)

Abstract

Abstract Splenic and bone marrow dendritic cells (DCs) and their subsets have been shown in multiple studies to play a critical role in maintaining tolerance and also in select differentiation of pathways responsive to infectious agents. Comparable studies in the liver have been lacking primarily due to difficulty in isolation and contradictory data. We have taken advantage of our ability to identify and isolate relatively pure DC populations and have compared the phenotype and function of select subsets of DCs in liver compared to spleen in C57BL/6 mice. Importantly, freshly isolated NK1.1−CD11c+ liver DC subsets (conventional and plasmacytoid DCs) can efficiently endocytose dextran as well as induce significant levels of TNF-α, IL-6 and IL-12 p40 in response to toll-like receptor ligand stimulation. These responses are higher than comparable studies of isolated splenic DCs from the same animals. In addition, there is a relatively higher frequency of pDC populations in liver. Our results suggest that hepatic DCs has differential capability in response to innate signals and that in fact CD11c+ hepatic DCs have a greater capacity to respond to innate stimulation but less capable of inducing CpG activated-allogeneic T cells. Our data emphasize not only the critical difference in hepatic DC subsets, but also highlight the need to study individual DC subsets in understanding the modulation of the immune response in the liver.