Spotlight on liver macrophages for halting liver disease progression and injury

References

• Guillot A, Tacke F. Liver macrophages: old dogmas and new insights. Hepatol Commun. 2019;3(6):730–743.
   PubMed Web of Science ®Google Scholar
• Heinrich L, Booijink R, Khurana A, et al. Lipoxygenases in chronic liver diseases: current insights and future perspectives. Trends Pharmacol Sci. 2022;43(3):188–205.
   PubMed Web of Science ®Google Scholar
• Khurana A, Sayed N, Allawadhi P, et al. It’s all about the spaces between cells: role of extracellular matrix in liver fibrosis. Ann Transl Med. 2021;9(8):728.
   PubMed Web of Science ®Google Scholar
• Yadav P, Khurana A, Bhatti JS, et al. Glucagon-like peptide 1 and fibroblast growth factor-21 in non-alcoholic steatohepatitis: an experimental to clinical perspective. Pharmacol Res. 2022;184:106426 8.
   Web of Science ®Google Scholar
• Kazankov K, Jørgensen SMD, Thomsen KL, et al. The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Nat Clin Pract Gastroenterol Hepatol. 2019;16(3):145–159.
   Google Scholar
• Krenkel O. Tacke F Liver macrophages in tissue homeostasis and disease. Nat Rev Immunol. 2017;17(5):306–321.
   PubMed Web of Science ®Google Scholar
• Blériot C, Ginhoux F. Understanding the heterogeneity of resident liver macrophages. Front Immunol. 2019;10:2694.
   PubMed Web of Science ®Google Scholar
• Tacke F. Targeting hepatic macrophages to treat liver diseases. J Hepatol. 2017;66(6):1300–1312.
   PubMed Web of Science ®Google Scholar
• Li H, Zhou Y, Wang H, et al. Crosstalk between liver macrophages and surrounding cells in nonalcoholic steatohepatitis. Front Immunol. 2020;11:1169.
   PubMed Web of Science ®Google Scholar
• Wang C, Ma C, Gong L, et al. Macrophage polarization and its role in liver disease. Front Immunol. 2021;12:803037.
   PubMedGoogle Scholar
• Isaacs-Ten A, Moreno-Gonzalez M, Bone C, et al. Metabolic regulation of macrophages by SIRT1 determines activation during cholestatic liver disease in mice. Cell Mol Gastroenterol Hepatol. 2022;13(4):1019–1039.
   PubMed Web of Science ®Google Scholar
• Ginhoux F, Guilliams M. Tissue-resident macrophage ontogeny and homeostasis. Immunity. 2016;44(3):439–449.
   PubMed Web of Science ®Google Scholar
• Zhang C, Yang M, Ericsson AC. Function of macrophages in disease: current understanding on molecular mechanisms. Front Immunol. 2021;12:620510.
   PubMed Web of Science ®Google Scholar
• Nati M, Chung KJ, Chavakis T. The role of innate immune cells in nonalcoholic fatty liver disease. J Innate Immun. 2022;14(1):31–41.
   PubMed Web of Science ®Google Scholar
• Kisseleva T, Brenner D. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat Rev Gastroenterol Hepatol. 2021;18(3):151–166.
   PubMed Web of Science ®Google Scholar
• Tsuchida T, Friedman SL. Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol. 2017;14(7):397–411.
   PubMed Web of Science ®Google Scholar
• Viola A, Munari F, Sánchez-Rodríguez R, et al. A. The metabolic signature of macrophage responses. Front Immunol. 2019;10:1462.
   PubMed Web of Science ®Google Scholar
• Barreby E, Chen P, Aouadi M. Macrophage functional diversity in NAFLD - more than inflammation. Nat Rev Endocrinol. 2022;18(8):461–472.
   PubMed Web of Science ®Google Scholar
• Dou L, Shi X, He X, et al. Macrophage phenotype and function in liver disorder. Front Immunol. 2019;10:3112.
   PubMed Web of Science ®Google Scholar
• Liaskou E, Zimmermann HW, Li KK, et al. Monocyte subsets in human liver disease show distinct phenotypic and functional characteristics. Hepatology. 2013;57(1):385–398.
   PubMed Web of Science ®Google Scholar
• Tacke F, Zimmermann HW. Macrophage heterogeneity in liver injury and fibrosis. J Hepatol. 2014;60(5):1090–1096.
   PubMed Web of Science ®Google Scholar
• Nahrendorf M, Swirski FK. Abandoning M1/M2 for a network model of macrophage function. Circ Res. 2016;119(3):414–417.
   PubMed Web of Science ®Google Scholar
• Murray PJ, Allen JE, Biswas SK, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014;41(1):14–20.
   PubMed Web of Science ®Google Scholar
• Blériot C, Chakarov S, Ginhoux F. Determinants of resident tissue macrophage identity and function. Immunity. 2020;52(6):957–970.
   PubMed Web of Science ®Google Scholar
• Shi C, Pamer EG. Monocyte recruitment during infection and inflammation. Nat Rev Immunol. 2011;11(11):762–774.
   PubMed Web of Science ®Google Scholar
• Chiu S, Bharat A. Role of monocytes and macrophages in regulating immune response following lung transplantation. Curr Opin Organ Transplant. 2016;21(3):239–245.
   PubMed Web of Science ®Google Scholar
• Scott CL, Zheng F, De Baetselier P, et al. Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells. Nat Commun. 2016;7(1):10321.
   PubMedGoogle Scholar
• Dal-Secco D, Wang J, Zeng Z, et al. A dynamic spectrum of monocytes arising from the in situ reprogramming of CCR2+ monocytes at a site of sterile injury. J Exp Med. 2015;212(4):447–456.
   PubMed Web of Science ®Google Scholar
• Hu X, Chen J, Wang L, et al. Crosstalk among Jak-STAT, Toll-like receptor, and ITAM-dependent pathways in macrophage activation. J Leukoc Biol. 2007;82(2):237–243.
   PubMed Web of Science ®Google Scholar
• Carlin LM, Stamatiades EG, Auffray C, et al. Nr4a1-dependent Ly6C(low) monocytes monitor endothelial cells and orchestrate their disposal. Cell. 2013;153(2):362–375.
   PubMed Web of Science ®Google Scholar
• Wang M, You Q, Lor K, et al. Chronic alcohol ingestion modulates hepatic macrophage populations and functions in mice. J Leukoc Biol. 2014;96(4):657–665.
   PubMed Web of Science ®Google Scholar
• Chu HX, Broughton BR, Kim HA, et al. Evidence that Ly6C(hi) monocytes are protective in acute ischemic stroke by promoting M2 macrophage polarization. Stroke. 2015;46(7):1929–1937.
   PubMed Web of Science ®Google Scholar
• Ramachandran P, Pellicoro A, Vernon MA, et al. Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis. Proc Natl Acad Sci U S A. 2012;109(46):E3186–3195.
   PubMed Web of Science ®Google Scholar
• Karlmark KR, Zimmermann HW, Roderburg C, et al. The fractalkine receptor CX₃CR1 protects against liver fibrosis by controlling differentiation and survival of infiltrating hepatic monocytes. Hepatology. 2010;52(5):1769–1782.
   PubMed Web of Science ®Google Scholar
• Pellicoro A, Aucott RL, Ramachandran P, et al. Elastin accumulation is regulated at the level of degradation by macrophage metalloelastase (MMP-12) during experimental liver fibrosis. Hepatology. 2012;55(6):1965–1975.
   PubMed Web of Science ®Google Scholar
• Roohani S, Tacke F. Liver injury and the macrophage issue: molecular and mechanistic facts and their clinical relevance. Int J Mol Sci. 2021;22(14):7249.
   PubMed Web of Science ®Google Scholar
• Triantafyllou E, Woollard KJ, McPhail MJW, et al. The role of monocytes and macrophages in acute and acute-on-chronic liver failure. Front Immunol. 2018;9:2948.
   PubMed Web of Science ®Google Scholar
• Bernal W, Wendon J. Acute liver failure. N Engl J Med. 2013;369(26):2525–2534.
   PubMed Web of Science ®Google Scholar
• Wang LX, Zhang SX, Wu HJ, et al. M2b macrophage polarization and its roles in diseases. J Leukoc Biol. 2019;106(2):345–358.
   PubMed Web of Science ®Google Scholar
• Murray PJ. Macrophage polarization. Annu Rev Physiol. 2017;79(1):541–566.
   PubMed Web of Science ®Google Scholar
• He Y, Gao Y, Zhang Q, et al. IL-4 Switches microglia/macrophage M1/M2 polarization and alleviates neurological damage by modulating the JAK1/STAT6 pathway following ICH. Neuroscience. 2020;437:161–171.
   PubMed Web of Science ®Google Scholar
• Juhas U, Ryba-Stanisławowska M, Szargiej P, et al. Different pathways of macrophage activation and polarization. Postepy Hig Med Dosw (Online). 2015;69:496–502.
   PubMedGoogle Scholar
• Xie J, Wu X, Zhou Q, et al. PICK1 confers anti-inflammatory effects in acute liver injury via suppressing M1 macrophage polarization. Biochimie. 2016;127:121–132.
   PubMed Web of Science ®Google Scholar
• Chen XX, Tang L, Fu YM, et al. Paralemmin-3 contributes to lipopolysaccharide-induced inflammatory response and is involved in lipopolysaccharide-Toll-like receptor-4 signaling in alveolar macrophages. Int J Mol Med. 2017;40(6):1921–1931.
   PubMed Web of Science ®Google Scholar
• Min L, Wang H, Qi H. Astragaloside IV inhibits the progression of liver cancer by modulating macrophage polarization through the TLR4/NF-κB/STAT3 signaling pathway. Am J Transl Res. 2022;14(3):1551.
   PubMed Web of Science ®Google Scholar
• Zhang J, Liu Y, Chen H, et al. MyD88 in hepatic stellate cells enhances liver fibrosis via promoting macrophage M1 polarization. Cell Death Dis. 2022;13(4):1–14.
   Web of Science ®Google Scholar
• Gong J, Li J, Dong H, et al. Inhibitory effects of berberine on proinflammatory M1 macrophage polarization through interfering with the interaction between TLR4 and MyD88. BMC Complement Altern Med. 2019;19(1):314.
   PubMed Web of Science ®Google Scholar
• Lu H, Wu L, Liu L, et al. Quercetin ameliorates kidney injury and fibrosis by modulating M1/M2 macrophage polarization. Biochem Pharmacol. 2018;154:203–212.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Cheng J, Su Y, et al. Cordycepin induces M1/M2 macrophage polarization to attenuate the liver and lung damage and immunodeficiency in immature mice with sepsis via NF-κB/p65 inhibition. J Pharm Pharmacol. 2022;74(2):227–235.
   PubMed Web of Science ®Google Scholar
• Wang J, Liu Y, Ding H, et al. Mesenchymal stem cell-secreted prostaglandin E(2) ameliorates acute liver failure via attenuation of cell death and regulation of macrophage polarization. Stem Cell Res Ther. 2021;12(1):15.
   PubMed Web of Science ®Google Scholar
• Tomar S, Zumbrun EE, Nagarkatti M, et al. Protective role of cannabinoid receptor 2 activation in galactosamine/lipopolysaccharide-induced acute liver failure through regulation of macrophage polarization and microRNAs. J Pharmacol Exp Ther. 2015;353(2):369–379.
   PubMed Web of Science ®Google Scholar
• Zhao J, Chen XD, Yan ZZ, et al. Gut-derived exosomes induce liver injury after intestinal ischemia/reperfusion by promoting hepatic macrophage polarization. Inflammation. 2022. Online ahead of print. DOI:10.1007/s10753-022-01695-0.
   Web of Science ®Google Scholar
• Gong W, Zhu H, Lu L, et al. A Benzenediamine analog FC-99 drives M2 macrophage polarization and alleviates lipopolysaccharide- (LPS-) induced liver injury. Mediators Inflamm. 2019;2019:7823069.
   PubMed Web of Science ®Google Scholar
• Liu J, Zhang S, Cao H, et al. Deficiency of p38α in macrophage ameliorates d-galactosamine/TNF-α-induced acute liver injury in mice. Febs J. 2017;284(24):4200–4215.
   PubMed Web of Science ®Google Scholar
• Peng J, Li J, Huang J, et al. p300/CBP inhibitor A-485 alleviates acute liver injury by regulating macrophage activation and polarization. Theranostics. 2019;9(26):8344–8361.
   PubMed Web of Science ®Google Scholar
• Canton M, Sánchez-Rodríguez R, Spera I, et al. Reactive oxygen species in macrophages: sources and targets. Front Immunol. 2021;12:734229.
   PubMed Web of Science ®Google Scholar
• Alharthi J, Latchoumanin O, George J, et al. Macrophages in metabolic associated fatty liver disease. World J Gastroenterol. 2020;26(16):1861.
   PubMed Web of Science ®Google Scholar
• Liu T, Liu F, Peng LW, et al. The peritoneal macrophages in inflammatory diseases and abdominal cancers. Oncol Res. 2018;26(5):817–826.
   PubMed Web of Science ®Google Scholar
• Kim E, Yang J, Beltran CD, et al. Role of spleen-derived monocytes/macrophages in acute ischemic brain injury. J Cereb Blood Flow Metab. 2014;34(8):1411–1419.
   PubMed Web of Science ®Google Scholar
• Li L, Wei W, Li Z, et al. The spleen promotes the secretion of CCL2 and supports an M1 dominant phenotype in hepatic macrophages during liver fibrosis. Cell Physiol Biochem. 2018;51(2):557–574. Erratum in: Cell Physiol Biochem. 52(6):1586-1587 (2019).
   PubMedGoogle Scholar
• Wen Y, Lambrecht J, Ju C, et al. Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities. Cell Mol Immunol. 2021;18(1):45–56.
   PubMed Web of Science ®Google Scholar
• Lazarus JV, Mark HE, Anstee QM, et al. Advancing the global public health agenda for NAFLD: a consensus statement. Nat Clin Pract Gastroenterol Hepatol. 2022;19(1):60–78.
   Google Scholar
• Xu L, Liu W, Bai F, et al. Hepatic macrophage as a key player in fatty liver disease. Front Immunol. 2021;12:708978.
   PubMed Web of Science ®Google Scholar
• Cheng D, Chai J, Wang H, et al. Hepatic macrophages: key players in the development and progression of liver fibrosis. Liver Int. 2021;41(10):2279–2294.
   PubMed Web of Science ®Google Scholar
• Park JW, Jeong G, Kim SJ, et al. Predictors reflecting the pathological severity of non-alcoholic fatty liver disease: comprehensive study of clinical and immunohistochemical findings in younger Asian patients. J Gastroenterol Hepatol. 2007;22(4):491–497.
   PubMed Web of Science ®Google Scholar
• Gadd VL, Skoien R, Powell EE, et al. The portal inflammatory infiltrate and ductular reaction in human nonalcoholic fatty liver disease. Hepatology. 2014;59(4):1393–1405.
   PubMed Web of Science ®Google Scholar
• Guo Q, Furuta K, Lucien F, et al. Integrin β(1)-enriched extracellular vesicles mediate monocyte adhesion and promote liver inflammation in murine NASH. J Hepatol. 2019;71(6):1193–1205.
   PubMed Web of Science ®Google Scholar
• Chen C, Yang RX, Xu HG. STING and liver disease. J Gastroenterol. 2012;56(8):704–712.
   Google Scholar
• Luo X, Li H, Ma L, et al. Expression of STING is increased in liver tissues from patients with NAFLD and promotes macrophage-mediated hepatic inflammation and fibrosis in mice. Gastroenterology. 2018;155(6):1971–1984.e1974.
   PubMed Web of Science ®Google Scholar
• Wang X, Rao H, Zhao J, et al. STING expression in monocyte-derived macrophages is associated with the progression of liver inflammation and fibrosis in patients with nonalcoholic fatty liver disease. Lab Invest. 2020;100(4):542–552.
   PubMed Web of Science ®Google Scholar
• Sun YY, Li XF, Meng XM, et al. Macrophage phenotype in liver Injury and tepair. Scand J Immunol. 2017;85(3):166–174.
   PubMed Web of Science ®Google Scholar
• Luo W, Xu Q, Wang Q, et al. Effect of modulation of PPAR-γ activity on Kupffer cells M1/M2 polarization in the development of non-alcoholic fatty liver disease. Sci Rep. 2017;7:44612–44612.
   PubMed Web of Science ®Google Scholar
• Sica A, Invernizzi P, Mantovani AJ. Macrophage plasticity and polarization in liver homeostasis and pathology. Hepatology. 2014;59(5):2034–2042.
   PubMed Web of Science ®Google Scholar
• Thomas JA, Pope C, Wojtacha D, et al. Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function. Hepatology. 2011;53(6):2003–2015.
   PubMed Web of Science ®Google Scholar
• Ma PF, Gao CC, Yi J, et al. Cytotherapy with M1-polarized macrophages ameliorates liver fibrosis by modulating immune microenvironment in mice. J Hepatol. 2017;67(4):770–779.
   PubMed Web of Science ®Google Scholar
• Acharya C, Bajaj JS. Hepatic encephalopathy and liver transplantation: the past, present, and future toward equitable access. Liver Transpl. 2021;27(12):1830–1843.
   PubMed Web of Science ®Google Scholar
• Vagefi PA, Bertsimas D, Hirose R, et al. The rise and fall of the model for end-stage liver disease score and the need for an optimized machine learning approach for liver allocation. Curr Opin Organ Transplant. 2020;25(2):122–125.
   PubMed Web of Science ®Google Scholar
• Anstee QM, Castera L, Loomba R. Impact of non-invasive biomarkers on hepatology practice: past, present and future. J Hepatol. 2022;76(6):1362–1378.
   PubMed Web of Science ®Google Scholar
• Fu S, Wu D, Jiang W, et al. Molecular biomarkers in drug-induced liver injury: challenges and future perspectives. Front Pharmacol. 2019;10:1667.
   PubMed Web of Science ®Google Scholar
• Grønbæk H, Rødgaard-Hansen S, Aagaard NK, et al. Macrophage activation markers predict mortality in patients with liver cirrhosis without or with acute-on-chronic liver failure (ACLF). J Hepatol. 2016;64(4):813–822.
   PubMed Web of Science ®Google Scholar
• Berdowska A, Zwirska-Korczala K. Neopterin measurement in clinical diagnosis. J Clin Pharm Ther. 2001;26(5):319–329.
   PubMed Web of Science ®Google Scholar
• Sucher R, Schroecksnadel K, Weiss G, et al. Neopterin, a prognostic marker in human malignancies. Cancer Lett. 2010;287(1):13–22.
   PubMed Web of Science ®Google Scholar
• Demirbas S, Cakir E, Akgul EO, et al. Elevated serum neopterin levels in Acetaminophen-induced liver injury. Environ Toxicol Pharmacol. 2011;31(1):165–170.
   PubMed Web of Science ®Google Scholar
• Craig DG, Lee P, Pryde EA, et al. Serum neopterin and soluble CD163 as markers of macrophage activation in paracetamol (Acetaminophen)-induced human acute liver injury. Aliment Pharmacol Ther. 2013;38(11–12):1395–1404.
   PubMed Web of Science ®Google Scholar
• Wang L, Zhu Y, Liu Y, et al. Serum neopterin and indoleamine 2, 3-dioxyg activity are promising biomarkers for presence and progression of hepatitis B. Pteridines. 2022;33(1):9–10.
   Web of Science ®Google Scholar
• Venereau E, De Leo F, Mezzapelle R, et al. HMGB1 as biomarker and drug target. Pharmacol Res. 2016;111:534–544.
   PubMed Web of Science ®Google Scholar
• Yamamoto T, Tajima Y. HMGB1 is a promising therapeutic target for acute liver failure. Expert Rev Gastroenterol Hepatol. 2017;11(7):673–682.
   PubMed Web of Science ®Google Scholar
• Zamora R, Barclay D, Yin J, et al. HMGB1 is a central driver of dynamic pro-inflammatory networks in pediatric acute liver failure induced by Acetaminophen. Sci Rep. 2019;9(1):1–11.
   PubMedGoogle Scholar
• Cheng X, Zhu J, Li Y, et al. Serum biomarkers of isoniazid‐induced liver injury: aminotransferases are insufficient, and OPN, L‐FABP and HMGB1 can be promising novel biomarkers. J Appl Toxicol. 2022;42(3):516–528.
   PubMed Web of Science ®Google Scholar
• Chen R, Kang R, Tang D. The mechanism of HMGB1 secretion and release. Exp Mol Med. 2022;54(2):91–102.
   PubMed Web of Science ®Google Scholar
• Korver S, Bowen J, Pearson K, et al. The application of cytokeratin-18 as a biomarker for drug-induced liver injury. Arch Toxicol. 2021;95(11):3435–3448.
   PubMed Web of Science ®Google Scholar
• Yang H, Xing Z, Shao H, et al. The expression of cytokeratin and apoptosis-related molecules in echinococcosis related liver injury. Mol Biochem Parasitol. 2022;248:111455.
   PubMed Web of Science ®Google Scholar
• Li M, Tang Y, Wu L, et al. The hepatocyte-specific HNF4α/miR-122 pathway contributes to iron overload-mediated hepatic inflammation. Blood. 2017;130(8):1041–1051.
   PubMed Web of Science ®Google Scholar
• Bakshi S, Kaur M, Saini N, et al. Altered expressions of circulating microRNAs 122 and 192 during antitubercular drug induced liver injury indicating their role as potential biomarkers. Hum Exp Toxicol. 2021;40(9):1474–1484.
   PubMed Web of Science ®Google Scholar
• Rupprechter SAE, Sloan DJ, Oosthuyzen W, et al. MicroRNA-122 and cytokeratin-18 have potential as a biomarkers of drug-induced liver injury in European and African patients on treatment for mycobacterial infection. Br J Clin Pharmacol. 2021;87(8):3206–3217.
   PubMed Web of Science ®Google Scholar
• Starkey Lewis PJ, Dear J, Platt V, et al. Circulating microRNAs as potential markers of human drug-induced liver injury. Hepatology. 2011;54(5):1767–1776.
   PubMed Web of Science ®Google Scholar
• Possamai LA, Thursz MR, Wendon JA, et al. Modulation of monocyte/macrophage function: a therapeutic strategy in the treatment of acute liver failure. J Hepatol. 2014;61(2):439–445.
   PubMed Web of Science ®Google Scholar
• Schmidt LE, Dalhoff K. Alpha-fetoprotein is a predictor of outcome in Acetaminophen-induced liver injury. Hepatology. 2005;41(1):26–31.
   PubMed Web of Science ®Google Scholar
• Lu CY, Changelian P, Unanue E. Alpha-fetoprotein inhibits macrophage expression of Ia antigens. J Immunol. 1984;132(4):1722–1727.
   PubMed Web of Science ®Google Scholar
• Schmidt LE, Dalhoff K. Serum phosphate is an early predictor of outcome in severe Acetaminophen-induced hepatotoxicity. Hepatology. 2002;36(3):659–665.
   PubMed Web of Science ®Google Scholar
• Possamai LA, Antoniades CG, Anstee QM, et al. Role of monocytes and macrophages in experimental and human acute liver failure. World J Gastroenterol. 2010;16(15):1811.
   PubMed Web of Science ®Google Scholar
• Llewellyn HP, Vaidya VS, Wang Z, et al. Evaluating the sensitivity and specificity of promising circulating biomarkers to diagnose liver injury in humans. Toxicol Sci. 2021;181(1):23–34.
   PubMed Web of Science ®Google Scholar
• Aithal GP, Guha N, Fallowfield J, et al. Biomarkers in liver disease: emerging methods and potential applications. Int J Hepatol. 2012;2012:437508.
   PubMedGoogle Scholar
• Senior JR. 13 - ‘Classic’ biomarkers of liver injury. In: Goodsaid F, Mattes WB, editors. The path from biomarker discovery to regulatory qualification. edn ed. San Diego: Academic Press; 2013. p. 111–128.
   Google Scholar
• Zhao R, Zhao H, Y-Q G, et al. Usefulness of noncontrast MRI-based radiomics combined clinic biomarkers in stratification of liver fibrosis. Can J Gastroenterol Hepatol. 2022;2022:2249447.
   PubMed Web of Science ®Google Scholar
• Oishi Y, Manabe I. Macrophages in inflammation, repair and regeneration. Int Immunol. 2018;30(11):511–528.
   PubMed Web of Science ®Google Scholar
• Lauterbach MA, Wunderlich FT. Macrophage function in obesity-induced inflammation and insulin resistance. Pflugers Arch. Pflug Arch Eur J Phy. 2017;469(3):385–396.
   PubMed Web of Science ®Google Scholar
• Nielsen MC, Hvidbjerg Gantzel R, Clària J, et al. Macrophage activation markers, CD163 and CD206, in acute-on-chronic liver failure. Cells. 2020;9(5):1175.
   Web of Science ®Google Scholar
• Alharthi J, Eslam M. Biomarkers of metabolic (dysfunction)-associated fatty liver disease: an update. J Clin Transl Hepatol. 2022;10(1):134–139.
   PubMed Web of Science ®Google Scholar
• Fabriek BO, Dijkstra CD, van den Berg TK. The macrophage scavenger receptor CD163. Immunobiology. 2005;210(2):153–160.
   PubMed Web of Science ®Google Scholar
• Z-J X, Gu Y, Wang C-Z, et al. The M2 macrophage marker CD206: a novel prognostic indicator for acute myeloid leukemia. Oncoimmunology. 2019;9(1):1683347–1683347.
   PubMed Web of Science ®Google Scholar
• Shoji H, Yoshio S, Mano Y, et al. Interleukin-34 as a fibroblast-derived marker of liver fibrosis in patients with non-alcoholic fatty liver disease. Sci Rep. 2016;6(1):28814.
   PubMedGoogle Scholar
• Kumagai E, Mano Y, Yoshio S, et al. Serum YKL-40 as a marker of liver fibrosis in patients with non-alcoholic fatty liver disease. Sci Rep. 2016;6(1):35282.
   PubMedGoogle Scholar
• Martinou E, Pericleous M, Stefanova I, et al. Diagnostic modalities of non-alcoholic fatty liver disease: from biochemical biomarkers to multi-Omics non-Invasive approaches. Diagnostics. 2022;12(2):407.
   Web of Science ®Google Scholar
• Sakamoto Y, Yoshio S, Doi H, et al. Serum soluble sialic acid-binding immunoglobulin-like lectin-7 concentration as an indicator of liver macrophage activation and advanced fibrosis in patients with non-alcoholic fatty liver disease. Hepatol Res. 2020;50(4):466–477.
   PubMed Web of Science ®Google Scholar
• Xue Q, Yan Y, Zhang R, et al. Regulation of iNOS on immune cells and its role in diseases. Int J Mol Sci. 2018;19(12):3805.
   PubMed Web of Science ®Google Scholar
• Liu XL, Pan Q, Cao HX, et al. Lipotoxic hepatocyte‐derived exosomal microRNA 192‐5p activates macrophages through rictor/Akt/forkhead box transcription factor O1 signaling in nonalcoholic fatty liver disease. Hepatology. 2020;72(2):454–469.
   PubMed Web of Science ®Google Scholar
• Cervantes-Alvarez E, Limon-de la Rosa N, Vilatoba M, et al. Galectin-3 is overexpressed in advanced cirrhosis and predicts post-liver transplant infectious complications. Liver Int. 2022;42(10):2260–2273. .
   PubMed Web of Science ®Google Scholar
• Henderson NC, Mackinnon AC, Farnworth SL, et al. Galectin-3 regulates myofibroblast activation and hepatic fibrosis. Proc Natl Acad Sci U S A. 2006;103(13):5060–5065.
   PubMed Web of Science ®Google Scholar
• Li LC, Li J, Gao J. Functions of galectin-3 and its role in fibrotic diseases. J Pharmacol Exp Ther. 2014;351(2):336–343.
   PubMed Web of Science ®Google Scholar
• Siwicki M, Gort-Freitas NA, Messemaker M, et al. Resident Kupffer cells and neutrophils drive liver toxicity in cancer immunotherapy. Sci Immunol. 2021;6(61):eabi7083.
   PubMed Web of Science ®Google Scholar
• Lee K-J, Kim M-Y, Han Y-H. Roles of heterogenous hepatic macrophages in the progression of liver diseases. BMB Rep. 2022;55(4):166.
   PubMed Web of Science ®Google Scholar
• Singh V, Khurana A, Allawadhi P, et al. Emerging role of PD-1/PD-L1 inhibitors in chronic liver diseases. Front Pharmacol. 2021;12:790963.
   PubMed Web of Science ®Google Scholar
• Thibaut R, Gage MC, Pineda‐Torra I, et al. Liver macrophages and inflammation in physiology and physiopathology of non‐alcoholic fatty liver disease. FEBS J. 2022;289(11):3024–3057.
   PubMed Web of Science ®Google Scholar
• Daemen S, Gainullina A, Kalugotla G, et al. Dynamic shifts in the composition of resident and recruited macrophages influence tissue remodeling in NASH. Cell Rep. 2021;34(2):108626.
   PubMed Web of Science ®Google Scholar
• Bartneck M, Koppe C, Fech V, et al. Roles of CCR2 and CCR5 for hepatic macrophage polarization in mice with liver parenchymal cell-specific NEMO deletion. Cell Mol Gastroenterol Hepatol. 2021;11(2):327–347.
   PubMed Web of Science ®Google Scholar
• Lai WY, Mueller A. Latest update on chemokine receptors as therapeutic targets. Biochem Soc Trans. 2021;49(3):1385–1395.
   PubMed Web of Science ®Google Scholar
• Tacke F, Weiskirchen R. Non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH)-related liver fibrosis: mechanisms, treatment and prevention. Ann Transl Med. 2021;9(8):729.
   PubMed Web of Science ®Google Scholar
• Attia SL, Softic S, Mouzaki M. Evolving role for pharmacotherapy in NAFLD/NASH. Clin Transl Sci. 2021;14(1):11–19.
   PubMed Web of Science ®Google Scholar
• Rowe IA, Wong VW-S, Loomba R. Treatment candidacy for pharmacologic therapies for NASH. Clin Gastroenterol Hepatol. 2022;20(6):1209–1217.
   PubMed Web of Science ®Google Scholar
• Wang T-Y, Wang R-F, Z-Y B, et al. Metabolic dysfunction-associated fatty liver disease: association with kidney disease. Nat Rev Nephrol. 2022;18(4):259–268.
   PubMed Web of Science ®Google Scholar
• Keshvari S, Genz B, Teakle N, et al. Therapeutic potential of macrophage colony-stimulating factor in chronic liver disease. Dis Model Mech. 2022;15(4):dmm049387.
   PubMed Web of Science ®Google Scholar
• Muñoz-Garcia J, Cochonneau D, Télétchéa S, et al. The twin cytokines interleukin-34 and CSF-1: masterful conductors of macrophage homeostasis. Theranostics. 2021;11(4):1568.
   PubMed Web of Science ®Google Scholar
• Bailey SR, Vatsa S, Larson RC, et al. Blockade or deletion of IFNγ reduces macrophage activation without compromising CAR T-cell function in hematologic malignancies. Blood Cancer Discovery. 2022;3(2):136–153.
   PubMedGoogle Scholar
• Ma J, Chen T, Mandelin J, et al. Regulation of macrophage activation. Cell Mol Life Sci. 2003;60(11):2334–2346.
   PubMed Web of Science ®Google Scholar
• Brenner C, Galluzzi L, Kepp O, et al. Decoding cell death signals in liver inflammation. J Hepatol. 2013;59(3):583–594.
   PubMed Web of Science ®Google Scholar
• Singanayagam A, Triantafyllou E. Macrophages in chronic liver failure: diversity, plasticity and therapeutic targeting. Front Immunol. 2021;12:661182.
   PubMed Web of Science ®Google Scholar
• Weiskirchen R, Tacke F. Liver fibrosis: from pathogenesis to novel therapies. Dig Dis. 2016;34(4):410–422.
   PubMed Web of Science ®Google Scholar
• Navik U, Sheth VG, Khurana A, et al. Methionine as a double-edged sword in health and disease: current perspective and future challenges. Ageing Res Rev. 2021;72:101500.
   PubMed Web of Science ®Google Scholar
• Singh V, Khurana A, Navik U, et al. Apoptosis and pharmacological therapies for targeting thereof for cancer therapeutics. Sci. 2022;4(2):15.
   Google Scholar
• Loomba R, Lawitz E, Mantry PS, et al. The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: a randomized, phase 2 trial. Hepatology. 2018;67(2):549–559.
   PubMed Web of Science ®Google Scholar
• Maradana MR, Yekollu SK, Zeng B, et al. Immunomodulatory liposomes targeting liver macrophages arrest progression of nonalcoholic steatohepatitis. Metabolism. 2018;78:80–94.
   PubMed Web of Science ®Google Scholar
• Wang H, Mehal W, Nagy LE, et al. Immunological mechanisms and therapeutic targets of fatty liver diseases. Cell Mol Immunol. 2021;18(1):73–91.
   PubMed Web of Science ®Google Scholar
• Jindal S, Chockalingam S, Ghosh SS, et al. Connexin and gap junctions: perspectives from biology to nanotechnology based therapeutics. Transl Res. 2021;235:144–167.
   PubMed Web of Science ®Google Scholar
• Bartneck M, Warzecha KT, Tacke F. Therapeutic targeting of liver inflammation and fibrosis by nanomedicine. Hepatobiliary Surg Nutr. 2014;3(6):364–376.
   PubMedGoogle Scholar
• Traber PG, Zomer E. Therapy of experimental NASH and fibrosis with galectin inhibitors. PLoS One. 2013;8(12):e83481.
   PubMed Web of Science ®Google Scholar
• Bukong TN, Iracheta-Vellve A, Saha B, et al. Inhibition of spleen tyrosine kinase activation ameliorates inflammation, cell death, and steatosis in alcoholic liver disease. Hepatology. 2016;64(4):1057–1071.
   PubMed Web of Science ®Google Scholar