Heterogeneity of Dendritic Cells in the Mouse Liver: Identification and Characterization of Four Distinct Populations

Abstract

Liver dendritic cells (DC) are believed to play important roles in liver immunity, autoimmunity, and in the regulation of hepatic allograft acceptance. However, limited information is available on the phenotypes and functions of DC in the liver. To address this issue, we isolated DC from murine liver using procedures that do not involve collagenase, and characterized the freshly isolated DC population that had not been subjected to in vitro expansion. Thence, based on the expression of CD4, B220, and CD11b, four subsets or groups of hepatic NK1.1−CD11c+ DC were identified with the following phenotypes: B220+CD4+, B220+CD4−, B220−CD11b+, and B220−CD11b−. Each subset was further characterized both phenotypically and functionally. In addition to unique phenotypic expression, each subset displayed different allostimulation capability in mixed lymphocyte reaction assays. All four groups developed DC morphology following in vitro culture with activation agents and synthesized distinct patterns of cytokines in response to different stimuli. Taken together, our results suggest that groups I and II are IFN-α-producing plasmacytoid DC, group III cells are myeloid-related DC, while group IV is a heterogenous population containing both myeloid- and lymphoid-related DC. Our results demonstrate the highly heterogeneous nature of hepatic DC, which is in agreement with the unique requirements for APC in the complex liver environment.

Liver Dendritic Cells Are Less Immunogenic Than Spleen Dendritic Cells because of Differences in Subtype Composition

“…Upon activation with CpG oligonucleotides, liver DC produced massive amounts of IL-12, consistent with a previous report (10). Surprisingly, however, the levels were ϳ10 times higher than those of spleen DC, further supporting the dichotomy between their functions (Fig.…”

“…Our phenotypic data differ considerably from that of a recent report by Lian et al (10) who showed several subtypes of myeloid and pDC, but did not identify lymphoid DC displaying CD8␣ or DEC205. There are two differences between our methods that may in part explain the discrepant results.…”

“…There was also an abundance of immature plasmacytoid B220 ϩ DC (Fig. 6) like those that have previously been found in the thymus, spleen, lymph nodes, bone marrow, and liver (10,16). Although the surface marker expression by liver pDC was homogeneous, it appeared that there may be subtypes of spleen pDC based on heterogeneous expression of Ly6-G as well as the maturation markers tested.…”

Critical roles of interferon regulatory factor 4 in CD11bhighCD8α–dendritic cell development

“…We also examined the level of plasmacytoid DCs in the IRF-4 Ϫ/Ϫ spleen. CD19 ϩ and NK1.1 ϩ cells were gated out to exclude B cells and natural killer (NK) cells, which are B220 ϩ and CD11c low , respectively (44). The proportion and the absolute number of CD11c int B220 ϩ plasmacytoid DCs in IRF-4 Ϫ/Ϫ spleen were not significantly different from those of the wild-type spleen (Fig.…”

Hepatic CD206-positive macrophages express amphiregulin to promote the immunosuppressive activity of regulatory T cells in HBV infection

“…Intrahepatic mononuclear cells were prepared according to previous publications with several modifications [18][19][20][21]. In brief, mice were killed by inhalation of carbon dioxide for an average of 5 min, following which, the abdomen was opened immediately, and the spleen was collected and put in ice-cold PBS.…”