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Published on: April 3, 2017
The Hepatic Crown-like Structure: A Focal Point for Macrophage Evolution and Disease Response in Steatotic Liver
Kyle Yuquimpo1, Ayobami Dare1, Isabel Aranzazu Pulido Ruiz1
1Department of Internal Medicine and Liver Center, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Insights
The hepatic crown-like structure (hCLS) is crucial in steatotic liver disease, processing lipids and regulating inflammation. It comprises diverse macrophages, impacting fibrosis and macrophage development.
Area of Science:
- Hepatology
- Immunology
- Cell Biology
Background:
- The hepatic crown-like structure (hCLS) is a macrophage aggregate around dying hepatocytes in steatotic liver disease.
- Initially viewed as an inflammatory response, hCLS is now recognized for its roles in lipid processing, inflammation, fibrosis, and macrophage development.
Purpose of the Study:
- To review critical findings on hCLSs.
- To elucidate the role of hCLSs in macrophage development and function within steatotic liver diseases.
Main Methods:
- Lineage tracing studies.
- Transcriptomic analysis.
- Macrophage phenotyping.
Main Results:
- hCLSs contain heterogeneous macrophages, primarily bone marrow-derived infiltrating macrophages (IMs) and Kupffer cells (KCs).
- Macrophage subtypes include Lipid-Associated Macrophages (LAMs) and LAM-like KCs, expressing specific surface proteins (e.g., GPNMB, TREM2, VSIG4).
- hCLSs are key in lipid handling and inflammation, with debated roles in fibrogenesis and matrix remodeling.
Conclusions:
- hCLSs are vital multicellular structures in steatotic liver disease.
- Understanding hCLS macrophage heterogeneity is crucial for therapeutic strategies.
- Further research is needed to clarify hCLS involvement in liver fibrosis.
Abstract:
The hepatic crown-like structure (hCLS) is a shell-like aggregate of macrophages surrounding a large lipid-laden dying hepatocyte. This feature was initially assumed to simply be a response to increased inflammatory stress during steatotic liver disease, but recent studies have shown that the hCLS is a critical site for lipid processing, inflammation regulation, fibrosis modulation and macrophage development. Furthermore, advances in lineage tracing and transcriptomic analysis have provided information on the nature of the macrophage subtypes present in the hCLS. The hCLS consists of a heterogeneous mixture of macrophages that arise largely from bone marrow-derived infiltrating macrophages (IMs) but also have some of the properties of Kupffer cells (KCs). Most of the cells are variations of Lipid-Associated Macrophages (LAMs) expressing surface proteins such as GPNMB, TREM2, CD9, CD36, CD63 and CD11c. In addition, a class of LAM-like KCs is also present and these typically express many of the LAM proteins along with KC lineage proteins such as VSIG4 and CLEC4F. The hCLS plays an important role in lipid disposition and inflammation but conflicting evidence appears to support roles in fibrogenesis, extracellular matrix remodeling, and matrix degradation. This review aims to describe the critical findings and discoveries made regarding hCLSs and their role in macrophage development and function in steatotic liver diseases.
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