@article{9c320013de8f4125bd966b4239da976b,
title = "Dynamic Shifts in the Composition of Resident and Recruited Macrophages Influence Tissue Remodeling in NASH",
abstract = "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.",
keywords = "CCR2, Cx3cr1, Kupffer cells, crown-like structures, diabetes, fibrosis, inflammation, lipid-associated macrophages, liver",
author = "Sabine Daemen and Anastasiia Gainullina and Gowri Kalugotla and Li He and Chan, {Mandy M.} and Beals, {Joseph W.} and Liss, {Kim H.} and Samuel Klein and Feldstein, {Ariel E.} and Finck, {Brian N.} and Artyomov, {Maxim N.} and Schilling, {Joel D.}",
note = "Funding Information: This work was supported by NIH grants RO1 DK11003401 (J.D.S.), ADA 118-IBS280 (J.D.S.), and R01 DK104735 (B.N.F.) and support from the Pershing Square Foundation (S.K.). The core services of the Diabetes Research Center (P30 DK020579) and the Nutrition and Obesity Research Center (P30 DK56341) at Washington University School of Medicine also supported this work. Conceptualization, S.D. G.K. and J.D.S.; Methodology S.D. G.K. A.G. M.A. and J.D.S.; Investigation, S.D. A.G. G.K. L.H. M.C. J.B. K.H.L. and J.D.S.; Writing – Original Draft, J.D.S.; Writing – Review & Editing, S.D. A.G. J.W.B. S.K. B.N.F. M.A. and J.D.S.; Revision Experiments, Review, and Editing, S.D. A.G. A.E.F. and J.D.S. A.E.F. is co-inventor on pending and issued patents filed by the Cleveland Clinic and UCSD that refer to the use of biomarkers and therapies in inflammatory and fibrotic disorders. Scientific Founder: Jecure Therapeutics, Elgia Therapeutics. Consultant/Advisory Board: Gilead, GSK, Merck, Ferring Pharmaceutical, Centurion BioPharma, Oppilan Pharma. The remaining authors have no interests to declare. Funding Information: This work was supported by NIH grants RO1 DK11003401 (J.D.S.), ADA 118-IBS280 (J.D.S.), and R01 DK104735 (B.N.F.) and support from the Pershing Square Foundation (S.K.). The core services of the Diabetes Research Center ( P30 DK020579 ) and the Nutrition and Obesity Research Center ( P30 DK56341 ) at Washington University School of Medicine also supported this work. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2021",
month = jan,
day = "12",
doi = "10.1016/j.celrep.2020.108626",
language = "English",
volume = "34",
journal = "Cell Reports",
issn = "2211-1247",
number = "2",
}