The complex function of macrophages and their subpopulations in metabolic injury associated fatty liver disease

Subramanian, Pallavi; Chavakis, Triantafyllos

doi:10.1113/jp283820

Cited by 2 publications

(2 citation statements)

References 77 publications

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“…Macrophages are innate immune cells, present in every organ of the body ( 85 ) and are the most abundant immune cell population in the liver ( 86 ). They ensure tissue integrity by phagocytosis of cellular debris, waste products and apoptotic cells ( 87 – 89 ), and act as first line defense against pathogens.…”

Section: Macrophage Subsets In the Livermentioning

confidence: 99%

Macrophages and platelets in liver fibrosis and hepatocellular carcinoma

Casari,

Siegl,

Deppermann

et al. 2023

Front. Immunol.

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During fibrosis, (myo)fibroblasts deposit large amounts of extracellular matrix proteins, thereby replacing healthy functional tissue. In liver fibrosis, this leads to the loss of hepatocyte function, portal hypertension, variceal bleeding, and increased susceptibility to infection. At an early stage, liver fibrosis is a dynamic and reversible process, however, from the cirrhotic stage, there is significant progression to hepatocellular carcinoma. Both liver-resident macrophages (Kupffer cells) and monocyte-derived macrophages are important drivers of fibrosis progression, but can also induce its regression once triggers of chronic inflammation are eliminated. In liver cancer, they are attracted to the tumor site to become tumor-associated macrophages (TAMs) polarized towards a M2- anti-inflammatory/tumor-promoting phenotype. Besides their role in thrombosis and hemostasis, platelets can also stimulate fibrosis and tumor development by secreting profibrogenic factors and regulating the innate immune response, e.g., by interacting with monocytes and macrophages. Here, we review recent literature on the role of macrophages and platelets and their interplay in liver fibrosis and hepatocellular carcinoma.

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Section: Macrophage Subsets In the Livermentioning

confidence: 99%

Macrophages and platelets in liver fibrosis and hepatocellular carcinoma

Casari,

Siegl,

Deppermann

et al. 2023

Front. Immunol.

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“…Recent high-resolution analytical techniques have evidenced a large phenotypic heterogeneity among MoMFs from human and rodent MASH livers. These phenotypes include "lipid-associated" macrophages (LAM), also known as NASH-associated macrophages (NAMs), "scar-associated" macrophages (SAMs) present in fibrotic niches, and monocyte-derived Kupffer cells (8). Although LAM/NAMs and SAMs share some similarities such as the expression of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) and CD9 (9)(10)(11)(12), it is still unclear how these cell subsets relate in supporting inflammation and fibrogenesis.…”

Section: Introductionmentioning

confidence: 99%

Role of the co-stimulatory molecule inducible T-cell co-stimulator ligand (ICOSL) in the progression of experimental metabolic dysfunction-associated steatohepatitis

Provera,

Ramavath,

Gadipudi

et al. 2023

Front. Immunol.

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Background and aimsInducible T-cell Co-Stimulator (ICOS) present on T-lymphocytes and its ligand ICOSL expressed by myeloid cells play multiple roles in regulating T-cell functions. However, recent evidence indicates that reverse signalling involving ICOSL is also important in directing the differentiation of monocyte-derived cells. In this study, we investigated the involvement of ICOS/ICOSL dyad in modulating macrophage functions during the evolution of metabolic dysfunction-associated steatohepatitis (MASH).ResultsIn animal models of MASH, ICOS was selectively up-regulated on CD8+ T-cells in parallel with an expansion of ICOSL-expressing macrophages. An increase in circulating soluble ICOSL was also evident in patients with MASH as compared to healthy individuals. ICOSL knockout (ICOSL-/-) mice receiving choline/methionine deficient (MCD) diet for 6 weeks had milder steatohepatitis than wild type mice. MASH improvement was confirmed in mice fed with cholesterol-enriched Western diet for 24 weeks in which ICOSL deficiency greatly reduced liver fibrosis along with the formation of crown-like macrophage aggregates producing the pro-fibrogenic mediators osteopontin (OPN) and galectin-3 (Gal-3). These effects associated with a selective shewing of F4-80+/CD11bhigh monocyte-derived macrophages (MoMFs) expressing the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) to CD11blow/F4-80+ cells positive for the Kupffer cell marker C-type lectin-like type 2 receptor (CLEC-2), thus indicating an increased MoMF maturation toward monocyte-derived Kupffer cells.ConclusionsThese results suggest that CD8+ T-cells interaction with monocyte-derived macrophages through ICOS/ICOSL critically supports a specific subset of TREM2+-expressing cells contributing to the evolution of steatohepatitis. The data also point ICOS/ICOSL dyad as a possible target for therapeutic interventions in MASH.

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The complex function of macrophages and their subpopulations in metabolic injury associated fatty liver disease

Abstract: support-information-section).

Cited by 2 publications

References 77 publications

Macrophages and platelets in liver fibrosis and hepatocellular carcinoma

Macrophages and platelets in liver fibrosis and hepatocellular carcinoma

Role of the co-stimulatory molecule inducible T-cell co-stimulator ligand (ICOSL) in the progression of experimental metabolic dysfunction-associated steatohepatitis

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