Fig. 6: The PR3-targeting protein IL-32γ protects against liver inflammation and fibrosis in mice treated with MASH.

a, Proteome profiling of a human cytokine array for co-immunoprecipitation of endogenously secreted PR3 in CM from LPS-stimulated (CM-LPS) and nonstimulated (CM-CTRL) THP-1 cells. b, A bar graph indicating the average signal intensities of framed spots on the array blots from a. Each red bracket in the cytokine array analysis indicates the location of interleukin (IL)-32. c, Univariate logistic regression analysis was conducted in a discovery cohort (n = 130) to identify patients ‘at-risk’ from MASH based on the gene expression of PR3-bound cytokines. d, The gene‒disease network for IL32 was examined via data from genome-wide association studies that focused on records with a significance level of P < 1 × 10⁻⁶. e, Human macrophage subset gene expression of IL32 based on the Single Cell Portal, Broad Institute. f, A Venn diagram illustrating the ability of PR3 to target the inflammatory cytokine IL-32 and its relationship with SERPINA1 and MASH pathogenesis. g, Relative mRNA expression of proinflammatory genes in primary KCs co-stimulated with LPS and recombinant human IL-32γ (rhIL-32γ; 100 ng/ml) for 6 h. h–j, BWs (h), LWs (i) and LBW ratios (j) of NCD-fed WT mice (n = 5), NCD-fed hIL-32γ Tg mice (n = 5), FFD-fed WT mice (n = 10) and FFD-fed Tg mice (n = 9). k,l, Detection of the serum ALT (k) and cholesterol (l) levels in each group. m, The appearance of freshly collected liver tissues and H&E staining of liver sections from each group. n, IHC staining image of CLEC4F-positive KCs in FFD-fed Tg mice and FFD-fed WT mice. o, BODIPY-stained liver sections from each group. Representative images of BODIPY-stained sections were selected, and BODIPY-positive areas (green, for lipid accumulation) and DAPI-positive areas (blue, for nuclei and normalization) were measured. p, Relative mRNA expression of proinflammatory genes in the hepatic tissues of each group. q, Representative images of Sirius red-stained liver sections from each group. Representative images of whole-body liver sections were analyzed for Sirius red-positive areas. r, Relative mRNA expression of profibrogenic genes in liver sections. The data are presented as the means ± s.d.; *^,#P < 0.05, **^,##P < 0.01, ***^,###P < 0.001 and ****^,####P < 0.0001 versus the control model. ns, not significant.