Fig 2: Construction of IRGPI: (A) Weighted Gene Co-expression Network Analysis (WGCNA) immune-related genes and their four modules based on their degree of co-expression. The number in the module indicates the correlation between the module genes, HCC, and the p-values. (B) Univariate Cox proportional hazard regression analysis screens out the genes that have the greatest impact on the survival time of HCC and hazard ratio. (C) K-M curves for high and low IRGPI groups in the TCGA cohort. Log rank test, p < 0.001. (D) K-M curves for high and low MAPT expression groups in the TCGA cohort. Log rank test, p < 0.001. (E) K-M curves for high and low CCL14 expression groups in the TCGA cohort. Log rank test, p < 0.001. (F) K-M curves for high and low GHR expression groups in the TCGA cohort. Log rank test, p < 0.001. (G) K-M curves for high and low CD5L expression groups in the TCGA cohort. Log rank test, p < 0.001. (H, I) Univariate and multivariate independent prognostic analyses of IRGPI.

Fig 3: The effect of CD5L treatment on HepG2 and QSG-7701 cells. (A) CD5L treatment decreased the proliferation rate of HepG2. (B) CD5L treatment did not affect QSG-7701 proliferation. (C) CD5L treatment decreased the cell percentage in G2/M phase of HepG2. (D) CD5L treatment did not affect the cell cycle of QSG-7701. (E,F) CD5L treatment did not affect apoptosis of HepG2 and QSG-7701. CD5L: CD5 molecular-like; FITC: Fluorescein Isothiocyanate; PI: Propidium iodide; ns: no significant; ∗P < 0.01.

Fig 4: Conserved and divergent responses to sustained atherogenic dyslipidemia.a, Plasma levels of cholesterol in dyslipidemic APOE cKO and D374Y mice with respective littermate controls, maintained on a high fat diet for 20 weeks. (APOE cKO n = 16 vs 11; and D374Y n = 7 vs 3). Plots are ± SEM, two-sided t-test b, Representative liver sections stained with ORO in APOE cKO and D374Y mice after 20 weeks on a high fat diet (scale bars = 100 μm, n = 2 vs 2 for D374Y and n = 3 vs 3 for APOE cKO, where n indicates a different mouse). c, Representative liver sections stained with H&E in APOE cKO and D374Y mice after 20 weeks on a high fat diet (scale bars = 100 μm, n = 2 vs 2 in each group where n indicates a different mouse).d, Unique and common upregulated genes in both strains at 8, 12, and 20 weeks on a high fat diet. Unique genes for each strain are indicated at the bottom. e, Flow cytometry of CLEC4F levels on Kupffer cells from female D374Y versus littermate control after 8 weeks of high fat diet. f, Heatmap of the 72 genes upregulated at all time points in both strains, expressed in 76 human single cell types. g, Flow cytometry plots showing percentages of blood and liver monocytes, and liver Kupffer cells in dyslipidemic D374Y mice given clodronate liposome or Dil liposomes control for 8 weeks while on a high fat diet. h, Immunohistochemistry of liver to detect CD5L production in control or clodronate treated D374Y mice after 8 weeks of high fat diet (scale bars = 100 μm). i, The 14 genes not affected by clodronate-induced Kupffer cells depletion, expressed in liver myeloid cell clusters. j, Correlation between plasma IL18BP and liver PCSK9 expression in humans.

Fig 5: CD5L and LGALS3BP have similar elution profiles to the exosome marker CD81. Plasma from “Donor 1” was submitted to size-exclusion chromatography and fractions 6–12 were analysed by NTA, flow cytometry and transmission electron microscopy (TEM). (a) NTA was performed on a NanoSight LM10 (software version 3.0). For flow cytometry, samples were coupled to 4 µm beads and incubated with primary antibodies against CD81 (1:10), CD5L (1:100) or LGALS3BP (1:1,000). The secondary antibody was conjugated to Alexa 488 was used at a 1:1,000 dilution. MFI: mean fluorescence intensity. (b) Fraction 6 from size-exclusion chromatography was submitted to cryo-EM and (c) immunostained with anti-CD5L antibodies conjugated to gold spheres of 20 nm.