Macrophages in Liver Disease

Macrophages play a critical role in the initiation and progression of liver diseases mainly alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). They produce pro-fibrotic mediators and chemokines that directly activate and recruit fibroblasts and other inflammatory cells, and control extracellular matrix (ECM) turnover by regulating the balance of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs). During enhanced recruitment, monocytes (precursor of macrophages) undergo differentiation into two broad but distinct subsets of macrophages that are categorized as classically-activated Ly6Chigh M1 macrophages or alternatively-activated Ly6Clow M2 macrophages. During liver injury, the initial inflammatory response is predominantly mediated by classically-activated or inflammatory macrophages. They produce pro-inflammatory cytokines and other mediators, such as tumor necrosis factor α (TNFα), interleukin (IL)-1 and -12, nitric oxide generating enzyme (iNOS), and reactive oxygen species (ROS), and lead to matrix degradation and tissue destruction. However, during the resolution phase of the injury, macrophages are polarized into a restorative M2 phenotype with a different cytokine and chemokine repertoire, including IL-10, transforming growth factor β (TGF-β), MMPs, TIMPs, arginase 1 (Arg1), and vascular epithelial growth factor (VEGF). These M2 tissue repair macrophages have anti-inflammatory effects, promote new blood-vessel formation (angiogenesis), ECM synthesis, and tissue remodeling. These two different subsets display tremendous plasticity, and various mechanisms and micro-environmental factors influence their polarization status. Since macrophages have different phenotypes and contrasting functions, depleting all macrophages can be deleterious as macrophages are also involved in the repair process and liver regeneration. Therefore, specific macrophage subsets might be important targets in promoting resolution of liver disease.

This Research Topic welcomes contributions in form of Original Research articles and Reviews that cover the following topics related to macrophages in liver diseases:

1. Macrophage homeostasis, plasticity and polarization during liver diseases.
2. The role of macrophages during the pathogenesis of liver disease.
3. Factors determining the fate of macrophages during liver disease pathogenesis.
4. Crosstalk of macrophages with ECM, other cell types and soluble factors.
5. Role of macrophages in portal hypertension, liver repair and regeneration, ageing and metabolic syndrome.
6. Role of tumor-associated macrophages and tumor microenvironment in liver disease progression.
7. Therapeutic (nano) targeting of macrophages for the diagnosis and treatment of liver diseases.