(A) The liver surface contour of TAA/leptin-treated mice was markedly irregular. (B) H&E examination of the livers of treated mice revealed a distorted hepatic architectural pattern. Regenerative nodules were seen (asterisks), bounded by fibrous septa (arrows). In addition, there was diffuse ductal proliferation (arrowheads). Masson trichrome and picric acid–Sirius red staining highlighted the collagen network surrounding and bridging the portal triads. Original magnification, ×10 (H&E and Masson trichrome); ×20 (picric acid–Sirius red). (C–E) Liver NPCs were analyzed by flow cytometry. The percentage of cells within selected gates is indicated. (C) Density plots of NPCs from normal and fibrotic liver. CD11c⁺ DCs increased in fibrotic livers. In addition, a CD11c^hi subpopulation expanded in fibrotic livers (arrow), which was rare in controls. Gr1⁺CD11b⁺ myeloid-derived cells and CD3⁺CD8⁺ T cells were also dramatically expanded in fibrotic livers. (D) DC subset analysis revealed a lower CD11c⁺B220⁺ plasmacytoid fraction and a higher CD11b⁺CD8^– fraction among FLDCs compared with NLDCs. (E) Liver CD11c⁺ cells were assayed for expression of DC surface markers. Histograms show that freshly isolated FLDCs were more mature than controls. (F) FACS-sorted CD11c⁺ DCs were cultured for 24 hours either alone or with supplemental CpG before analysis for MHC II expression by flow cytometry. Median fluorescence is shown. There was considerably higher MHC II expression in FLDCs compared with NLDCs (P < 0.05). Isotype staining was similar for both groups (not shown). Phenotypic studies were repeated 4 times.