Fig. 6: Enhanced inflammation and cholesterol crystallization in LXRαW441R/W441R mice.
a, Immunohistochemical assessment of macrophage abundance (CD68, F4/80) and stellate cell activation (αSMA), in WD-fed WT and homozygous knock-in mice (W441R Hom). b–d, Quantitation of immunohistochemical staining. Statistical analysis was conducted with Kruskal–Wallis test with post hoc Dunn’s test. n(WT) = 8, n(Het) = 14, n(Hom) = 10 (b); n(WT) = 9, n(Het) = 14, n(Hom) = 10 (c); n(WT) = 11, n(Het) = 14, n(Hom) = 9 (d). e, Representative low-power images from frozen sections of livers from WT, LXRα knockout mice (LXR-KO) and homozygous knock-in (W441R Hom) mice viewed under a polarized light demonstrating presence of cholesterol crystals in the LXRα KO mice, which seems to spare steatotic regions and homozygous knock-in livers where cholesterol crystals are diffusely abundant. f, Ordinal grading of cholesterol crystal content conducted by a histopathologist blinded to genotype. 0, absent; 1, minimal; 2, marked but patchy or moderate and diffuse; 3, marked and diffuse. n = 3 animals per group. g, H&E staining of LXRα KO and WT livers demonstrating patchy inflammatory infiltrate mirroring the pattern of cholesterol crystal accumulation. h,i, IL-1-β measured in liver lysates from WT and homozygous knock-in mice (Hom) fed WD for 8 weeks, n = 9 per group (h) or homozygous knock-in mice fed WD for 8 weeks treated with either a control virus (GFP) or a virus expressing LXRα in hepatocytes, which rescues liver injury (Fig. 5), n = 6 males and four females per group. Analysis in h was conducted by Mann–Whitney U-test and by two-way ANOVA in i. The height of the bars represent mean ± s.d. All P values are two-sided. ***P = 0.0002 WT versus Hom (b); **P = 0.001 WT versus Hom (c); ***P = 0.0006, WT versus Hom, NS, P > 0.05 (d); P < 0.0001 (h).
