The Role of Resident and Circulatory Immune Cells in Pathogenesis and Resolution of Liver Fibrosis

Abstract

The liver is a non-immunological organ that has important functions in the body, including detoxification, regulating metabolic processes, and immune regulation. Several different immune cells constitute a crucial part of the liver as they participate in tissue homeostasis and pathogenesis. Multiple factors affect hepatic integrity, including tissue injury, alcohol consumption, and immune dysregulation, which start with inflammation and then progresses from the acute phase to chronic fibrosis and end up with carcinoma. Hepatic stellate cells and myofibroblasts are the main cells that participate in hepatic fibrosis as a result of abnormal changes, deposition of extracellular matrix proteins, and hepatocyte apoptosis. Innate cells, including macrophages, dendritic cells, neutrophils, eosinophils and innate lymphoid cells, also play an essential role in liver fibrosis. In addition to cellular involvement in homeostasis and disease conditions, non-cellular components, such as proinflammatory cytokines and anti-inflammatory cytokines, are significantly involved. Furthermore, signalling pathways such as tumour growth factor, oxidative stress, and inflammasome NOD-like receptor-caspase-1 are also involved during liver fibrosis. Therefore, immunotherapy for hepatic fibrosis primarily targets all these factors through cellular-based immunotherapy or cytokines-based immunotherapy, which in turn inhibits immune cells or inactivates cytokine secretion and signalling pathways. This review discusses the role of resident and circulatory immune cells in liver homeostasis and pathogenesis.