Crosstalk Between Autophagy and Innate Immunity: A Pivotal Role in Hepatic Fibrosis

Abstract

Liver fibrosis is a repair process of chronic liver injuries induced by toxic substances, pathogens, and inflammation, which exhibits a feature such as deposition of the extracellular matrix. The initiation and progression of liver fibrosis heavily relies on excessive activation of hepatic stellate cells (HSCs). The activated HSCs express different kinds of chemokine receptors to further promote matrix remodulation. The long-term progression of liver fibrosis will contribute to dysfunction of the liver and ultimately cause hepatocellular carcinoma. The liver also has abundant innate immune cells, including DCs, NK cells, NKT cells, neutrophils, and Kupffer cells, which conduct complicated functions to activation and expansion of HSCs and liver fibrosis. Autophagy is one specific type of cell death, by which the aberrantly expressed protein and damaged organelles are transferred to lysosomes for further degradation, playing a crucial role in cellular homeostasis. Autophagy is also important to innate immune cells in various aspects. The previous studies have shown that dysfunction of autophagy in hepatic immune cells can result in the initiation and progression of inflammation in the liver, directly or indirectly causing activation of HSCs, which ultimately accelerate liver fibrosis. Given the crosstalk between innate immune cells, autophagy, and fibrosis progression is complicated, and the therapeutic options for liver fibrosis are quite limited, the exploration is essential. Herein, we review the previous studies about the influence of autophagy and innate immunity on liver fibrosis and the molecular mechanism to provide novel insight into the prevention and treatment of liver fibrosis.

Autoimmunity and Carcinogenesis: Their Relationship under the Umbrella of Autophagy

“…The vast majority of lymphocytes engulfed by phagocytosis in liver cells are CD8+ T cells and are mainly observed in the area of caspase-3-induced apoptosis [ 399 ]. NK cells are involved in liver fibrosis [ 400 ]. HSCs impair the killing effect of NK cells by TGFβ secretion [ 401 ].…”

Anti‐inflammatory effect and mechanism of catalpol in various inflammatory diseases

“…Liver fibrosis (HF) is an important link in the progression of chronic inflammation in the liver to cirrhosis and hepatocellular carcinoma, therefore, effective suppression of the inflammatory response is the key to the treatment of HF (Chen et al, 2022). Autophagy, an inflammationrelated defense mechanism in chronic liver disease, is considered a new target for the treatment of liver fibrosis (Chen et al, 2022). Liu et al…”

“…Liver fibrosis (HF) is an important link in the progression of chronic inflammation in the liver to cirrhosis and hepatocellular carcinoma, therefore, effective suppression of the inflammatory response is the key to the treatment of HF (Chen et al, 2022). Autophagy, an inflammation‐related defense mechanism in chronic liver disease, is considered a new target for the treatment of liver fibrosis (Chen et al, 2022). Liu et al showed that catalpol significantly inhibited the release of inflammatory cytokines by activating autophagy, thereby suppressing the inflammatory response and ultimately alleviating liver fibrosis (Liu et al, 2018).…”

Machine learning and experimental validation identified autophagy signature in hepatic fibrosis

“…Studies indicate that an imbalance in the immune microenvironment of the liver is the main driver of liver fibrosis ( 12 ). Autophagy, which is regulated by a diverse array of immune cells, plays a role in managing the liver’s immune microenvironment ( 13 , 14 ). Analysis of immune cell infiltration provides insights into the distribution and quantity of immune cells within liver tissue.…”