Abstract

Ample evidence suggests that hepatic macrophages play key roles in the injury and repair mechanisms during liver disease progression. There are two major populations of hepatic macrophages: the liver resident Kupffer cells and the monocyte-derived macrophages, which rapidly infiltrate the liver during injury. Under different disease conditions, the tissue microenvironmental cues of the liver critically influence the phenotypes and functions of hepatic macrophages. Furthermore, hepatic macrophages interact with multiple cells types in the liver, such as hepatocytes, neutrophils, endothelial cells, and platelets. These crosstalk interactions are of paramount importance in regulating the extents of liver injury, repair, and ultimately liver disease progression. In this review, we summarize the novel findings highlighting the impact of injury-induced microenvironmental signals that determine the phenotype and function of hepatic macrophages. Moreover, we discuss the role of hepatic macrophages in homeostasis and pathological conditions through crosstalk interactions with other cells of the liver.

Highlights

  • Hepatic macrophages, consisting of liver resident Kupffer cells (KCs) and monocyte-derived macrophages (MoMφs), play a central role in maintaining homeostasis of the liver as well as contributing to the progression of acute or chronic liver injury [1]

  • We summarize the latest findings about specific environmental signals that impact the phenotype and function of hepatic macrophages and discuss the functions of hepatic macrophages in healthy and diseased liver through interacting with other cells

  • With regard to the maintenance of tissue-resident macrophages including KCs, an interesting “niche competition” model has been put forth. This model proposes that bone marrow–derived circulating monocytes and erythromyeloid progenitors (EMPs) have an almost identical potential to develop into KCs and that they compete for a restricted number of niches

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Summary

Hepatic Macrophages in Liver Injury

Specialty section: This article was submitted to Molecular Innate Immunity, a section of the journal

Frontiers in Immunology
INTRODUCTION
ORIGIN OF HEPATIC MACROPHAGES
IMPACT OF TISSUE MICROENVIRONMENTAL FACTORS ON HEPATIC MACROPHAGES
PAMPs Phagocytosis of cellular debris
Phagocytosis of Dead Cells
COMMUNICATION BETWEEN HEPATIC MACROPHAGES AND OTHER CELLS IN THE LIVER
MoMφs cholangiocytes cholangiocytes LSECs NKT cells NKT cells
Crosstalk Between Hepatic Macrophages and Hepatocytes
Findings
Interactions of Macrophages With Other Hepatic Immune Cells
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