https://orcid.org/0000-0002-0749-4555
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ABSTRACT
Introduction
Over the past two decades, understanding of hepatic macrophage biology has provided astounding details of their role in the progression and regression of liver diseases. The hepatic macrophages constitute resident macrophages, Kupffer cells, and circulating bone marrow monocyte-derived macrophages, which play a diverse role in liver injury and repair. Imbalance in the macrophage population leads to pathological consequences and is responsible for the initiation and progression of acute and chronic liver injuries. Further, distinct populations of hepatic macrophages and their high heterogeneity make their complex role enigmatic. The unique features of distinct phenotypes of macrophages have provided novel biomarkers for defining the stages of liver diseases. The distinct mechanisms of hepatic macrophages polarization and recruitment have been at the fore front of research. In addition, the secretome of hepatic macrophages and their immune regulation has provided clinically relevant therapeutic targets.
Areas covered
Herein, we have highlighted the current understanding in the area of hepatic macrophages, and their role in the progression of liver injury.
Expert opinion
It is essential to ascertain the physiological and pathological role of evolutionarily conserved distinct macrophage phenotypes in different liver diseases before viable approaches may see a clinical translation.
Article highlights
Hepatic macrophages constitute resident macrophages, Kupffer cells, and circulating bone marrow monocyte-derived macrophages.
Imbalance in the hepatic macrophage population leads to pathological consequences.
The secretome of hepatic macrophages and their immune regulation is critical for halting the progression of liver diseases.
Interfering with the activation of Kupffer cells is an intriguing approach to halt the progression of liver diseases.
Promoting M1 to M2 polarization can hasten restoration of hepatic injury.
This box summarizes key points contained in the article.
List of abbreviations
| ACLF | = | acute-on-chronic liver failure |
| AFP | = | α-fetoprotein |
| ALF | = | acute liver failure |
| ALI | = | acute liver injury |
| ALT | = | alanine aminotransferase |
| ASK1 | = | apoptosis signal-regulating kinase 1 |
| AST | = | aspartate aminotransferase |
| CB2 | = | cannabinoid receptor 2 |
| ccCK-18 | = | caspase-cleaved form of CK-18 |
| CK-18 | = | cytokeratin-18 |
| CLD(s) | = | chronic liver disease(s) |
| CLI | = | chronic liver injury |
| CSF1R | = | colony-stimulating factor 1 receptor |
| CX3CL1 | = | chemokine (C-X3-C motif) ligand 1 |
| CXCL | = | chemokine ligand |
| cyPGs | = | cyclopentenone PGs |
| DAMP(s) | = | damage-associated molecular pattern(s) |
| DILI | = | Drug-induced liver injury |
| ECM | = | extracellular matrix |
| FoxO1 | = | forkhead box transcription factor O1 |
| GC | = | glucocorticosteroids |
| GGT | = | gamma-glutamyltransferase |
| GILZ | = | GCs-induced leucine zipper |
| HCC | = | hepatocellular carcinoma |
| HIF | = | hypoxia inducible factor |
| HSC(s) | = | hepatic stellate cell(s) |
| HMGB1 | = | High mobility group box 1 |
| iNOS | = | nitric oxide synthase |
| i/R | = | ischemia/reperfusion |
| ITGβ1Ab | = | integrin β1 neutralizing antibody |
| JAK | = | Janus kinase |
| KC(s) | = | Kupffer cell(s) |
| L-FABP | = | liver-fatty acid-binding protein |
| LPS | = | lipopolysaccharide |
| LSEC(s) | = | liver sinusoidal endothelial cell(s) |
| LT8s) | = | leukotriene(s) |
| MMP | = | matrix metalloproteinase |
| MSC | = | mesenchymal stem cell |
| MoMFs | = | monocyte-derived macrophages |
| MyD88 | = | myeloid differentiation factor 88 |
| NAFLD | = | non-alcoholic fatty liver disease |
| NASH | = | non-alcoholic steatohepatitis |
| NF-κB | = | nuclear factor kappa-B |
| NP(s) | = | nanoparticle(s) |
| OPN | = | osteopontin |
| PAMP(s) | = | pathogen-associated molecular pattern(s) |
| PG(s) | = | prostaglandin(s) |
| PGE2 | = | prostaglandin E2 |
| PM(s) | = | peritoneal macrophages |
| PMC(s) | = | peritoneal macrophage(s) |
| PRR(s) | = | pattern recognition receptor(s) |
| Rictor | = | rapamycin-insensitive companion of mammalian target of rapamycin |
| ROS | = | reactive oxygen species |
| sCD163 | = | soluble CD163 |
| scRNA-seq | = | single-cell RNA sequencing |
| Siglac-7 | = | sialic acid binding immunoglobulin-like lectin-7 |
| sSiglac-7 | = | soluble Siglec-7 |
| STAT | = | signal transducers and activators of transcription |
| STING | = | stimulator of interferon genes |
| SYK | = | spleen tyrosine kinase |
| TAK1 | = | TGF-β-activated kinase 1 |
| TGF-β1 | = | transforming growth factor beta 1 |
| Th1 | = | helper T cell 1 |
| Th2 | = | helper T cell 2 |
| TLR | = | toll-like receptor |
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.