Cirrhosis has multiple etiologies and initial triggers. However, common features during pathogenesis of this disease are the development of hepatic inflammation and the development of fibrosis. Both resident liver macrophages (Kupffer cells) and infiltrating monocyte-derived macrophages play a central role in the initiation and maintenance of inflammation, as well as in fibrogenesis, through the activation of hepatic stellate cells. To exert these diverse functions, these macrophages are naturally highly versatile cells that can adapt their activation status according to cues from their microenvironment (e.g. lipotoxic molecules, cytokines, danger signals, necrotic cell debris). Importantly, macrophages can also revert towards a restorative phenotype by promoting tissue repair, by dampening inflammation and regression of fibrosis upon withdrawal of the insult.
While the diversity of macrophage phenotypes and their differential contribution to disease pathogenesis within the liver has been extensively reviewed, it is unclear how myeloid-derived cells in the circulation or from other organ sites contribute to cirrhosis-associated complications or disease progression in the liver. For example, patients with advanced stages of cirrhosis often exhibit a dysfunctional intestinal barrier, whereby luminal bacteria and their products ‘leak’ into the circulation and reach the liver via the portal vein (gut-liver axis). Exactly how intestinal macrophages contributes to barrier break-down and how circulating monocytes are affected by the chronic exposure to bacterial products are clinically relevant questions since cirrhosis patients frequently succumb to systemic infections. Additionally, in the context of Non-alcoholic Fatty Liver Disease (NAFLD), adipose tissue-derived macrophages play a prominent role as regulators of inflammation and metabolism. Cross-talk between adipose tissue and the liver has also been implicated in the pathogenesis of NAFLD. Nevertheless, the exact mechanism or nature of secreted factors that consequently fuels inflammation and fibrosis in the liver is unknown.
In this Research Topic, we welcome the submission of Original Research, Review, Mini-Review and Opinion articles that cover different aspects of monocyte and macrophage involvement during alcoholic and non-alcoholic liver disease. We specifically encourage studies that cover, but are not limited to, to the following topics:
1. The role of intestinal myeloid-derived cells in promoting bacterial translocation during cirrhosis.
2. Dysfunction of circulating monocytes but also neutrophils during cirrhosis and acute or chronic liver failure.
3. New therapeutic strategies targeting myeloid-derived cells in patients with alcoholic or non-alcoholic liver disease.
4. Adipose tissue-derived myeloid cells during NAFLD pathogenesis.
Cirrhosis has multiple etiologies and initial triggers. However, common features during pathogenesis of this disease are the development of hepatic inflammation and the development of fibrosis. Both resident liver macrophages (Kupffer cells) and infiltrating monocyte-derived macrophages play a central role in the initiation and maintenance of inflammation, as well as in fibrogenesis, through the activation of hepatic stellate cells. To exert these diverse functions, these macrophages are naturally highly versatile cells that can adapt their activation status according to cues from their microenvironment (e.g. lipotoxic molecules, cytokines, danger signals, necrotic cell debris). Importantly, macrophages can also revert towards a restorative phenotype by promoting tissue repair, by dampening inflammation and regression of fibrosis upon withdrawal of the insult.
While the diversity of macrophage phenotypes and their differential contribution to disease pathogenesis within the liver has been extensively reviewed, it is unclear how myeloid-derived cells in the circulation or from other organ sites contribute to cirrhosis-associated complications or disease progression in the liver. For example, patients with advanced stages of cirrhosis often exhibit a dysfunctional intestinal barrier, whereby luminal bacteria and their products ‘leak’ into the circulation and reach the liver via the portal vein (gut-liver axis). Exactly how intestinal macrophages contributes to barrier break-down and how circulating monocytes are affected by the chronic exposure to bacterial products are clinically relevant questions since cirrhosis patients frequently succumb to systemic infections. Additionally, in the context of Non-alcoholic Fatty Liver Disease (NAFLD), adipose tissue-derived macrophages play a prominent role as regulators of inflammation and metabolism. Cross-talk between adipose tissue and the liver has also been implicated in the pathogenesis of NAFLD. Nevertheless, the exact mechanism or nature of secreted factors that consequently fuels inflammation and fibrosis in the liver is unknown.
In this Research Topic, we welcome the submission of Original Research, Review, Mini-Review and Opinion articles that cover different aspects of monocyte and macrophage involvement during alcoholic and non-alcoholic liver disease. We specifically encourage studies that cover, but are not limited to, to the following topics:
1. The role of intestinal myeloid-derived cells in promoting bacterial translocation during cirrhosis.
2. Dysfunction of circulating monocytes but also neutrophils during cirrhosis and acute or chronic liver failure.
3. New therapeutic strategies targeting myeloid-derived cells in patients with alcoholic or non-alcoholic liver disease.
4. Adipose tissue-derived myeloid cells during NAFLD pathogenesis.
