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The complex myeloid network of the liver with diverse functional capacity at steady state and in inflammation.

Eckert C, Klein N, Kornek M, Lukacs-Kornek V - Front Immunol (2015)

Bottom Line: In recent years, it has been an explosion of information regarding the role of various myeloid cells in liver pathology.The complexity of myeloid cell populations and the missing exclusive marker combination make the interpretation of the data often extremely difficult.Moreover, the review outlines the currently known marker combinations for the identification of these cell populations for the study of their role in liver immunology.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine II, Saarland University Medical Center , Homburg , Germany.

ABSTRACT
In recent years, it has been an explosion of information regarding the role of various myeloid cells in liver pathology. Macrophages and dendritic cell (DC) play crucial roles in multiple chronic liver diseases such as fibrosis and non-alcoholic fatty liver disease (NAFLD). The complexity of myeloid cell populations and the missing exclusive marker combination make the interpretation of the data often extremely difficult. The current review aims to summarize the multiple roles of macrophages and DCs in chronic liver diseases, especially pointing out how these cells influence liver immune and parenchymal cells thereby altering liver function and pathology. Moreover, the review outlines the currently known marker combinations for the identification of these cell populations for the study of their role in liver immunology.

No MeSH data available.


Related in: MedlinePlus

The contribution of DCs and macrophages to the pathomechanism of liver fibrosis and NASH. Liver injury triggers the activation of Kuppfer cells, the resident macrophage population of the liver. Their activation leads to the release of inflammatory mediators and chemokines such as TNF, IL-1β, and CCL2. This is followed by the recruitment of various immune cells involving inflammatory monocytes and DCs. The Ly6Chi monocytes differentiate into M1 CCR9+iNOS+ macrophages, and together with DCs in the progression phase of liver injury, act in a pro-inflammatory manner and perpetuate inflammation. Some DCs, possibly the LL-DCs, seem to inhibit liver steatohepatitis and protect liver damage. In resolution, the Ly6Clow restorative macrophages together with MMP9+ DCs promote fibrolysis and the restoration of normal tissue architecture. HMGB-1, high mobility group box-1 protein; HSC, hepatic stellate cells; KC, Kupffer cells; LL-DC, low lipid containing DCs; LSEC, liver sinusoidal endothelial cells.
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Figure 1: The contribution of DCs and macrophages to the pathomechanism of liver fibrosis and NASH. Liver injury triggers the activation of Kuppfer cells, the resident macrophage population of the liver. Their activation leads to the release of inflammatory mediators and chemokines such as TNF, IL-1β, and CCL2. This is followed by the recruitment of various immune cells involving inflammatory monocytes and DCs. The Ly6Chi monocytes differentiate into M1 CCR9+iNOS+ macrophages, and together with DCs in the progression phase of liver injury, act in a pro-inflammatory manner and perpetuate inflammation. Some DCs, possibly the LL-DCs, seem to inhibit liver steatohepatitis and protect liver damage. In resolution, the Ly6Clow restorative macrophages together with MMP9+ DCs promote fibrolysis and the restoration of normal tissue architecture. HMGB-1, high mobility group box-1 protein; HSC, hepatic stellate cells; KC, Kupffer cells; LL-DC, low lipid containing DCs; LSEC, liver sinusoidal endothelial cells.

Mentions: Taken together, the liver represents a unique immunological niche within the body. Its parenchymal and non-parenchymal cells guard its tolerogenic and suppressive microenvironment while supporting its sentinel task of the portal and systemic circulation (Figure 1). Most liver injuries trigger the activation of resident KC/macrophage population that rapidly releases pro-inflammatory mediators such as TNF and IL-1β. This is followed by a chain of events that seem to be commonly shared by many injuries causing NASH and leading to liver fibrosis. The response involves the alterations within the myeloid cell composition primarily affecting macrophages. Importantly, other immune cells such as DCs, neutrophils, innate cells, and activated T cell are also recruited to the injured liver and play various roles in disease progression (6, 97). The exact role of liver DCs during chronic liver injury is yet to be determined. Nevertheless, they seem to be similarly pro-inflammatory as the Ly6Chi recruited monocytes. This feature is shared with infectious liver diseases; thus, it supposes to induce liver protecting immunity (2, 7). During chronic liver diseases, the overwhelming presence of pro-inflammatory immune cells together with liver damaging noxious agents eventually lead to extensive cell death and scar formation, a common outcome for chronic liver disorders. While KC activation alarms other immune cells to travel to the liver, it influences metabolic processes and survival of hepatocytes. During disease progression, Ly6Chi cells seem to develop into Ly6Clo restorative macrophages. These cells, if the harmful agent vanishes, lead to resolution and can restore normal tissue architecture (Figure 1). Especially, in this process, DCs are complementing the macrophage population. In infection, recent report demonstrated that necroptosis of KCs was necessary to induce the Th2 mediated tissue repair (106) that remains to be tested to affect fibrosis resolution in the future. Equally important is the more detailed understanding of the factors involved in the switch from the pro-inflammatory to the restorative macrophage population.


The complex myeloid network of the liver with diverse functional capacity at steady state and in inflammation.

Eckert C, Klein N, Kornek M, Lukacs-Kornek V - Front Immunol (2015)

The contribution of DCs and macrophages to the pathomechanism of liver fibrosis and NASH. Liver injury triggers the activation of Kuppfer cells, the resident macrophage population of the liver. Their activation leads to the release of inflammatory mediators and chemokines such as TNF, IL-1β, and CCL2. This is followed by the recruitment of various immune cells involving inflammatory monocytes and DCs. The Ly6Chi monocytes differentiate into M1 CCR9+iNOS+ macrophages, and together with DCs in the progression phase of liver injury, act in a pro-inflammatory manner and perpetuate inflammation. Some DCs, possibly the LL-DCs, seem to inhibit liver steatohepatitis and protect liver damage. In resolution, the Ly6Clow restorative macrophages together with MMP9+ DCs promote fibrolysis and the restoration of normal tissue architecture. HMGB-1, high mobility group box-1 protein; HSC, hepatic stellate cells; KC, Kupffer cells; LL-DC, low lipid containing DCs; LSEC, liver sinusoidal endothelial cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4403526&req=5

Figure 1: The contribution of DCs and macrophages to the pathomechanism of liver fibrosis and NASH. Liver injury triggers the activation of Kuppfer cells, the resident macrophage population of the liver. Their activation leads to the release of inflammatory mediators and chemokines such as TNF, IL-1β, and CCL2. This is followed by the recruitment of various immune cells involving inflammatory monocytes and DCs. The Ly6Chi monocytes differentiate into M1 CCR9+iNOS+ macrophages, and together with DCs in the progression phase of liver injury, act in a pro-inflammatory manner and perpetuate inflammation. Some DCs, possibly the LL-DCs, seem to inhibit liver steatohepatitis and protect liver damage. In resolution, the Ly6Clow restorative macrophages together with MMP9+ DCs promote fibrolysis and the restoration of normal tissue architecture. HMGB-1, high mobility group box-1 protein; HSC, hepatic stellate cells; KC, Kupffer cells; LL-DC, low lipid containing DCs; LSEC, liver sinusoidal endothelial cells.
Mentions: Taken together, the liver represents a unique immunological niche within the body. Its parenchymal and non-parenchymal cells guard its tolerogenic and suppressive microenvironment while supporting its sentinel task of the portal and systemic circulation (Figure 1). Most liver injuries trigger the activation of resident KC/macrophage population that rapidly releases pro-inflammatory mediators such as TNF and IL-1β. This is followed by a chain of events that seem to be commonly shared by many injuries causing NASH and leading to liver fibrosis. The response involves the alterations within the myeloid cell composition primarily affecting macrophages. Importantly, other immune cells such as DCs, neutrophils, innate cells, and activated T cell are also recruited to the injured liver and play various roles in disease progression (6, 97). The exact role of liver DCs during chronic liver injury is yet to be determined. Nevertheless, they seem to be similarly pro-inflammatory as the Ly6Chi recruited monocytes. This feature is shared with infectious liver diseases; thus, it supposes to induce liver protecting immunity (2, 7). During chronic liver diseases, the overwhelming presence of pro-inflammatory immune cells together with liver damaging noxious agents eventually lead to extensive cell death and scar formation, a common outcome for chronic liver disorders. While KC activation alarms other immune cells to travel to the liver, it influences metabolic processes and survival of hepatocytes. During disease progression, Ly6Chi cells seem to develop into Ly6Clo restorative macrophages. These cells, if the harmful agent vanishes, lead to resolution and can restore normal tissue architecture (Figure 1). Especially, in this process, DCs are complementing the macrophage population. In infection, recent report demonstrated that necroptosis of KCs was necessary to induce the Th2 mediated tissue repair (106) that remains to be tested to affect fibrosis resolution in the future. Equally important is the more detailed understanding of the factors involved in the switch from the pro-inflammatory to the restorative macrophage population.

Bottom Line: In recent years, it has been an explosion of information regarding the role of various myeloid cells in liver pathology.The complexity of myeloid cell populations and the missing exclusive marker combination make the interpretation of the data often extremely difficult.Moreover, the review outlines the currently known marker combinations for the identification of these cell populations for the study of their role in liver immunology.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine II, Saarland University Medical Center , Homburg , Germany.

ABSTRACT
In recent years, it has been an explosion of information regarding the role of various myeloid cells in liver pathology. Macrophages and dendritic cell (DC) play crucial roles in multiple chronic liver diseases such as fibrosis and non-alcoholic fatty liver disease (NAFLD). The complexity of myeloid cell populations and the missing exclusive marker combination make the interpretation of the data often extremely difficult. The current review aims to summarize the multiple roles of macrophages and DCs in chronic liver diseases, especially pointing out how these cells influence liver immune and parenchymal cells thereby altering liver function and pathology. Moreover, the review outlines the currently known marker combinations for the identification of these cell populations for the study of their role in liver immunology.

No MeSH data available.


Related in: MedlinePlus