Figure 4.

Lanifibranor treatment reduces hepatocyte injury, inflammatory cytokine, and circulating immune cell recruitment in the LoC. A) Wild‐type CICs were perfused for 30 min into the LoC after APAP‐, FFA‐, or FFA and lanifibranor treatment, and the remaining cells from the perfusate were analyzed by multispectral flow cytometry. The dynamically perfused culture medium may be collected at the end of the experiment and used for further measurements including cytokine and transaminase measurement. AST activity was measured in the LoC exposed to B) acetaminophen, or C) FFAs and lanifibranor. Circulating cytokine levels measured in the perfusate from the LoC exposed to D) acetaminophen, or E) FFAs and lanifibranor. CIC depletion (migration score) from the LoC perfusate after F) APAP or G) FFA with or without lanifibranor treatment is shown for the respective immune cell types. Relative changes in absolute cell numbers as compared to the appropriate vehicle conditions. Sample sizes: B–E) n = 4 per group, F,G) n = 3 per group. Abbreviations: A or APAP: acetaminophen; AST: aspartate aminotransferase; CCL2: Chemokine (C‐C motif) ligand 2; CICs: circulating immune cells; DCs: dendritic cells; F or FFAs: free fatty acids; FL or FFAs + Lanif: free fatty acids plus lanifibranor; FACS: fluorescence‐activated cell sorting; GM‐CSF: granulocyte‐macrophage colony‐stimulating factor; HSCs: hepatic stellate cells; IFN: interferon; IL: interleukin; IU: international units; KCs: Kupffer cells; LSECs: liver sinusoidal endothelial cells; NK: natural killer; TNF‐α: tumor necrosis factor‐alpha; V or Veh: vehicle. One‐way ANOVA followed by Tukey's multiple comparison test and paired student's t‐tests were performed. *p < 0.05 as indicated or as compared to vehicle.