Dynamic Shifts in the Composition of Resident and Recruited Macrophages Influence Tissue Remodeling in NASH
Summary: Macrophage-mediated inflammation is critical in the pathogenesis of non-alcoholic steatohepatitis (NASH). Here, we describe that, with high-fat, high-sucrose-diet feeding, mature TIM4pos Kupffer cells (KCs) decrease in number, while monocyte-derived Tim4neg macrophages accumulate. In concer...
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doaj-2d415d29b48b4ca78ceb4721531288bc2021-01-14T04:17:07ZengElsevierCell Reports2211-12472021-01-01342108626Dynamic Shifts in the Composition of Resident and Recruited Macrophages Influence Tissue Remodeling in NASHSabine Daemen0Anastasiia Gainullina1Gowri Kalugotla2Li He3Mandy M. Chan4Joseph W. Beals5Kim H. Liss6Samuel Klein7Ariel E. Feldstein8Brian N. Finck9Maxim N. Artyomov10Joel D. Schilling11Diabetes Research Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USADepartment of Medicine, Washington University School of Medicine, St. Louis, MO, USA; ITMO University, Saint Petersburg, RussiaDiabetes Research Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USADiabetes Research Center, Washington University School of Medicine, St. Louis, MO, USADepartment of Medicine, Washington University School of Medicine, St. Louis, MO, USACenter for Human Nutrition, Washington University School of Medicine, St. Louis, MO, USADiabetes Research Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, USACenter for Human Nutrition, Washington University School of Medicine, St. Louis, MO, USADepartment of Pediatrics, University of California, San Diego, San Diego, CA, USADiabetes Research Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, USADepartment of Medicine, Washington University School of Medicine, St. Louis, MO, USADiabetes Research Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA; Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, USA; Corresponding authorSummary: Macrophage-mediated inflammation is critical in the pathogenesis of non-alcoholic steatohepatitis (NASH). Here, we describe that, with high-fat, high-sucrose-diet feeding, mature TIM4pos Kupffer cells (KCs) decrease in number, while monocyte-derived Tim4neg macrophages accumulate. In concert, monocyte-derived infiltrating macrophages enter the liver and consist of a transitional subset that expresses Cx3cr1/Ccr2 and a second subset characterized by expression of Trem2, Cd63, Cd9, and Gpmnb; markers ascribed to lipid-associated macrophages (LAMs). The Cx3cr1/Ccr2-expressing macrophages, referred to as C-LAMs, localize to macrophage aggregates and hepatic crown-like structures (hCLSs) in the steatotic liver. In C-motif chemokine receptor 2 (Ccr2)-deficient mice, C-LAMs fail to appear in the liver, and this prevents hCLS formation, reduces LAM numbers, and increases liver fibrosis. Taken together, our data reveal dynamic changes in liver macrophage subsets during the pathogenesis of NASH and link these shifts to pathologic tissue remodeling.http://www.sciencedirect.com/science/article/pii/S2211124720316156Kupffer cellsinflammationdiabetesliverCCR2crown-like structures |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sabine Daemen Anastasiia Gainullina Gowri Kalugotla Li He Mandy M. Chan Joseph W. Beals Kim H. Liss Samuel Klein Ariel E. Feldstein Brian N. Finck Maxim N. Artyomov Joel D. Schilling |
spellingShingle |
Sabine Daemen Anastasiia Gainullina Gowri Kalugotla Li He Mandy M. Chan Joseph W. Beals Kim H. Liss Samuel Klein Ariel E. Feldstein Brian N. Finck Maxim N. Artyomov Joel D. Schilling Dynamic Shifts in the Composition of Resident and Recruited Macrophages Influence Tissue Remodeling in NASH Cell Reports Kupffer cells inflammation diabetes liver CCR2 crown-like structures |
author_facet |
Sabine Daemen Anastasiia Gainullina Gowri Kalugotla Li He Mandy M. Chan Joseph W. Beals Kim H. Liss Samuel Klein Ariel E. Feldstein Brian N. Finck Maxim N. Artyomov Joel D. Schilling |
author_sort |
Sabine Daemen |
title |
Dynamic Shifts in the Composition of Resident and Recruited Macrophages Influence Tissue Remodeling in NASH |
title_short |
Dynamic Shifts in the Composition of Resident and Recruited Macrophages Influence Tissue Remodeling in NASH |
title_full |
Dynamic Shifts in the Composition of Resident and Recruited Macrophages Influence Tissue Remodeling in NASH |
title_fullStr |
Dynamic Shifts in the Composition of Resident and Recruited Macrophages Influence Tissue Remodeling in NASH |
title_full_unstemmed |
Dynamic Shifts in the Composition of Resident and Recruited Macrophages Influence Tissue Remodeling in NASH |
title_sort |
dynamic shifts in the composition of resident and recruited macrophages influence tissue remodeling in nash |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2021-01-01 |
description |
Summary: Macrophage-mediated inflammation is critical in the pathogenesis of non-alcoholic steatohepatitis (NASH). Here, we describe that, with high-fat, high-sucrose-diet feeding, mature TIM4pos Kupffer cells (KCs) decrease in number, while monocyte-derived Tim4neg macrophages accumulate. In concert, monocyte-derived infiltrating macrophages enter the liver and consist of a transitional subset that expresses Cx3cr1/Ccr2 and a second subset characterized by expression of Trem2, Cd63, Cd9, and Gpmnb; markers ascribed to lipid-associated macrophages (LAMs). The Cx3cr1/Ccr2-expressing macrophages, referred to as C-LAMs, localize to macrophage aggregates and hepatic crown-like structures (hCLSs) in the steatotic liver. In C-motif chemokine receptor 2 (Ccr2)-deficient mice, C-LAMs fail to appear in the liver, and this prevents hCLS formation, reduces LAM numbers, and increases liver fibrosis. Taken together, our data reveal dynamic changes in liver macrophage subsets during the pathogenesis of NASH and link these shifts to pathologic tissue remodeling. |
topic |
Kupffer cells inflammation diabetes liver CCR2 crown-like structures |
url |
http://www.sciencedirect.com/science/article/pii/S2211124720316156 |
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