CHARACTERISATION OF KUPFFER CELL AND INFILTRATING MONO-MACROPHAGE POPULATIONS IN CCl4 INDUCED LIVER DAMAGE model

Background Kupffer cells (KC) are embryonically derived liver resident macrophages, responsible for maintaining liver homeostasis. Apart from KCs, infiltrating mono-macrophages of bone marrow origin also make up a small proportion of the hepatic macrophage population. During chronic liver diseases, the Kupffer cell population is largely replaced by the infiltrating mono-macrophage populations. Thus, the hepatic macrophage populations differ in their origin, phenotype, and characteristics. So, maintaining a balance between the different hepatic macrophage populations determines the outcome of the progression of chronic liver diseases. Aim To study the miRNA-based epigenetic dysregulation of KCs and infiltrating macrophages during chronic liver diseases. Methods- C57BL/6 mice were intraperitoneally injected with carbon tetrachloride (CCl4) twice a week for 4 and 18 weeks to induce progressive liver damage. Enzymatic digestion of the liver using collagenase was performed to isolate non-parenchymal cell fractions (NPF). Cell sorting using specific surface antibodies was performed to isolate KCs and infiltrating mono-macrophages from the NPF of digested livers. Results The overall leukocyte cell population was found to be slightly increased in the CCl4 groups than oil-treated group. The overall frequency of the myeloid cell population remained the same between the vehicle and CCl4-treated groups. The frequency of KCs is decreased in both CCl4-treated mice liver groups (20%-25% of total myeloid cell population) in comparison to the vehicle-treated group (60% of myeloid cell population), while the frequency of mono-macrophages was found to be initially increased in the 4 weeks CCl4 treated group (25% of myeloid cells) and then decreased in the 18 weeks CCl4 treated group (10% of myeloid cells). Conclusion Our preliminary results suggest a dynamic change in the hepatic macrophage populations during chronic liver disease conditions. During the initial stage of CCl4-induced liver disease, the loss of the KC population is replenished by the infiltrating mono-macrophages. Our next step is to fully characterize the sorted KCs and infiltrating mono-macrophages, at the epigenetic level, and potentially correlate these alterations with the chronic progression of liver disease toward hepatocellular carcinoma.

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Ajith, A., Evraerts, J., Brusa, D., Bouzin, C., Sokal, E., & Najimi, M. (2023). CHARACTERISATION OF KUPFFER CELL AND INFILTRATING MONO-MACROPHAGE POPULATIONS IN CCl4 INDUCED LIVER DAMAGE model. Télévie symposium UCLouvain, Brussels, Belgium. https://hdl.handle.net/2078.5/101561