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Front Immunol. 2019 Dec 4;10:2840. doi: 10.3389/fimmu.2019.02840. eCollection 2019.

Macrophages in Zebrafish Models of Liver Diseases.

Shwartz A1, Goessling W1,2,3,4,5,6, Yin C7.

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Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Harvard Stem Cell Institute, Cambridge, MA, United States.
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States.
Broad Institute, Massachusetts Institute of Technology and Harvard, Cambridge, MA, United States.
Division of Health Sciences and Technology, Harvard and Massachusetts Institute of Technology, Boston, MA, United States.
Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Division of Gastroenterology, Hepatology and Nutrition and Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.


Hepatic macrophages are key components of the liver immunity and consist of two main populations. Liver resident macrophages, known as Kupffer cells in mammals, are crucial for maintaining normal liver homeostasis. Upon injury, they become activated to release proinflammatory cytokines and chemokines and recruit a large population of inflammatory monocyte-derived macrophages to the liver. During the progression of liver diseases, macrophages are highly plastic and have opposing functions depending on the signaling cues that they receive from the microenvironment. A comprehensive understanding of liver macrophages is essential for developing therapeutic interventions that target these cells in acute and chronic liver diseases. Mouse studies have provided the bulk of our current knowledge of liver macrophages. The emergence of various liver disease models and availability of transgenic tools to visualize and manipulate macrophages have made the teleost zebrafish (Danio rerio) an attractive new vertebrate model to study liver macrophages. In this review, we summarize the origin and behaviors of macrophages in healthy and injured livers in zebrafish. We highlight the roles of macrophages in zebrafish models of alcoholic and non-alcoholic liver diseases, hepatocellular carcinoma, and liver regeneration, and how they compare with the roles that have been described in mammals. We also discuss the advantages and challenges of using zebrafish to study liver macrophages.


ALD; NAFLD; hepatocellular carcinoma; kupffer cells; monocytes; regeneration

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