The complex function of macrophages and their subpopulations in metabolic injury associated fatty liver disease.
NASH
SkeyNAFLD
inflammation
macrophages
Journal
The Journal of physiology
ISSN: 1469-7793
Titre abrégé: J Physiol
Pays: England
ID NLM: 0266262
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
received:
27
11
2022
accepted:
15
02
2023
medline:
3
4
2023
pubmed:
25
2
2023
entrez:
24
2
2023
Statut:
ppublish
Résumé
Non-alcoholic fatty liver disease (NAFLD), recently also defined as metabolic dysfunction-associated fatty liver disease (MAFLD), is a major health problem, as it affects ∼25% of the population globally and is a major cause of hepatic cirrhosis and thereby liver failure, as well as hepatocellular carcinoma. MALFD comprises a broad range of pathological conditions in the liver, including simple fat accumulation (steatosis) and the more progressive non-alcoholic steatohepatitis (NASH) that can lead to fibrosis development. Cells of innate immunity, and particularly macrophages, comprising the liver resident Kupffer cells and the recruited monocyte-derived macrophages, play complex roles in NASH-related inflammation and disease progression to fibrosis. Here, we discuss the recent developments with regards to the function of liver macrophage subpopulations during MAFLD development and progression.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1159-1171Informations de copyright
© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.
Références
Aizarani, N., Saviano, A., Sagar, M. L., Durand, S., Herman, J. S., Pessaux, P., Baumert, T. F., & Grun, D. (2019). A human liver cell atlas reveals heterogeneity and epithelial progenitors. Nature, 572, 99-204.
Alzaid, F., Lagadec, F., Albuquerque, M., Ballaire, R., Orliaguet, L., Hainault, I., Blugeon, C., Lemoine, S., Lehuen, A., Saliba, D. G., Udalova, I. A., Paradis, V., Foufelle, F., & Venteclef, N. (2016). IRF5 governs liver macrophage activation that promotes hepatic fibrosis in mice and humans. JCI Insight, 1(20), e88689.
Andrews, T. S., Atif, J., Liu, J. C., Perciani, C. T., Ma, X. Z., Thoeni, C., Slyper, M., Eraslan, G., Segerstolpe, A., Manuel, J., Chung, S., Winter, E., Cirlan, I., Khuu, N., Fischer, S., Rozenblatt-Rosen, O., Regev, A., McGilvray, I. D., Bader, G. D., & MacParland, S. A. (2022). Single-cell, single-nucleus, and spatial RNA sequencing of the human liver identifies cholangiocyte and mesenchymal heterogeneity. Hepatology Communications, 6(4), 821-840.
Angulo, P., Kleiner, D. E., Dam-Larsen, S., Adams, L. A., Bjornsson, E. S., Charatcharoenwitthaya, P., Mills, P. R., Keach, J. C., Lafferty, H. D., Stahler, A., Haflidadottir, S., & Bendtsen, F. (2015). Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology, 149(2), 389-397.e10.
Barreby, E., Chen, P., & Aouadi, M. (2022). Macrophage functional diversity in NAFLD - More than inflammation. Nature Reviews Endocrinology, 18(8), 461-472.
Beattie, L., Sawtell, A., Mann, J., Frame, T. C. M., Teal, B., de Labastida Rivera, F., Brown, N., Walwyn-Brown, K., Moore, J. W. J., MacDonald, S., Lim, E. K., Dalton, J. E., Engwerda, C. R., MacDonald, K. P., & Kaye, P. M. (2016). Bone marrow-derived and resident liver macrophages display unique transcriptomic signatures but similar biological functions. Journal of Hepatology, 65(4), 758-768.
Bieghs, V., Verheyen, F., van Gorp, P. J., Hendrikx, T., Wouters, K., Lutjohann, D., Gijbels, M. J., Febbraio, M., Binder, C. J., Hofker, M. H., & Shiri-Sverdlov, R. (2012). Internalization of modified lipids by CD36 and SR-A leads to hepatic inflammation and lysosomal cholesterol storage in Kupffer cells. PLoS ONE, 7(3), e34378.
Bieghs, V., Walenbergh, S. M., Hendrikx, T., van Gorp, P. J., Verheyen, F., Olde Damink, S. W., Masclee, A. A., Koek, G. H., Hofker, M. H., Binder, C. J., & Shiri-Sverdlov, R. (2013). Trapping of oxidized LDL in lysosomes of Kupffer cells is a trigger for hepatic inflammation. Liver International, 33(7), 1056-1061.
Cai, B., Dongiovanni, P., Corey, K. E., Wang, X., Shmarakov, I. O., Zheng, Z., Kasikara, C., Davra, V., Meroni, M., Chung, R. T., Rothlin, C. V., Schwabe, R. F., Blaner, W. S., Birge, R. B., Valenti, L., & Tabas, I. (2020). Macrophage MerTK promotes liver fibrosis in nonalcoholic steatohepatitis. Cell Metabolism, 31(2), 406-421.e7.
Castoldi, A., Monteiro, L. B., van Teijlingen Bakker, N., Sanin, D. E., Rana, N., Corrado, M., Cameron, A. M., Hassler, F., Matsushita, M., Caputa, G., Klein Geltink, R. I., Buscher, J., Edwards-Hicks, J., Pearce, E. L., & Pearce, E. J. (2020). Triacylglycerol synthesis enhances macrophage inflammatory function. Nature Communications, 11(1), 4107.
Chu, P. S., Nakamoto, N., Ebinuma, H., Usui, S., Saeki, K., Matsumoto, A., Mikami, Y., Sugiyama, K., Tomita, K., Kanai, T., Saito, H., & Hibi, T. (2013). C-C motif chemokine receptor 9 positive macrophages activate hepatic stellate cells and promote liver fibrosis in mice. Hepatology, 58(1), 337-350.
Chung, K. W., Lee, E. K., Kim, D. H., An, H. J., Kim, N. D., Im, D. S., Lee, J., Yu, B. P., & Chung, H. Y. (2015). Age-related sensitivity to endotoxin-induced liver inflammation: Implication of inflammasome/IL-1beta for steatohepatitis. Aging Cell, 14(4), 524-533.
Daemen, S., Chan, M. M., & Schilling, J. D. (2021). Comprehensive analysis of liver macrophage composition by flow cytometry and immunofluorescence in murine NASH. STAR Protocols, 2(2), 100511.
Daemen, S., Gainullina, A., Kalugotla, G., He, L., Chan, M. M., Beals, J. W., Liss, K. H., Klein, S., Feldstein, A. E., Finck, B. N., Artyomov, M. N., & Schilling, J. D. (2021). Dynamic shifts in the composition of resident and recruited macrophages influence tissue remodeling in NASH. Cell Reports, 34(2), 108626.
Deppermann, C., Kratofil, R. M., Peiseler, M., David, B. A., Zindel, J., Castanheira, F., van der Wal, F., Carestia, A., Jenne, C. N., Marth, J. D., & Kubes, P. (2020). Macrophage galactose lectin is critical for Kupffer cells to clear aged platelets. Journal of Experimental Medicine, 217(4), e20190723.
Diehl, A. M., & Day, C. (2017). Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis. New England Journal of Medicine, 377(21), 2063-2072.
Eslam, M., Sanyal, A. J., & George, J., International Consensus P. (2020). MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology, 158(7), 1999-2014 e1991.
Francque, S. M., Bedossa, P., Ratziu, V., Anstee, Q. M., Bugianesi, E., Sanyal, A. J., Loomba, R., Harrison, S. A., Balabanska, R., Mateva, L., Lanthier, N., Alkhouri, N., Moreno, C., Schattenberg, J. M., Stefanova-Petrova, D., Vonghia, L., Rouzier, R., Guillaume, M., … Group N. S. (2021). A randomized, controlled trial of the Pan-PPAR agonist lanifibranor in NASH. New England Journal of Medicine, 385(17), 1547-1558.
Fred, R. G., Steen Pedersen, J., Thompson, J. J., Lee, J., Timshel, P. N., Stender, S., Opseth Rygg, M., Gluud, L. L., Bjerregaard Kristiansen, V., Bendtsen, F., Hansen, T., & Pers, T. H. (2022). Single-cell transcriptome and cell type-specific molecular pathways of human non-alcoholic steatohepatitis. Scientific Reports, 12(1), 13484.
Friedman, S. L., Ratziu, V., Harrison, S. A., Abdelmalek, M. F., Aithal, G. P., Caballeria, J., Francque, S., Farrell, G., Kowdley, K. V., Craxi, A., Simon, K., Fischer, L., Melchor-Khan, L., Vest, J., Wiens, B. L., Vig, P., Seyedkazemi, S., Goodman, Z., Wong, V. W., … Lefebvre, E. (2018). A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis. Hepatology, 67(5), 1754-1767.
Gomez Perdiguero, E., Klapproth, K., Schulz, C., Busch, K., Azzoni, E., Crozet, L., Garner, H., Trouillet, C., de Bruijn, M. F., Geissmann, F., & Rodewald, H. R. (2015). Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Nature, 518(7540), 547-551.
Govaere, O., Petersen, S. K., Martinez-Lopez, N., Wouters, J., Van Haele, M., Mancina, R. M., Jamialahmadi, O., Bilkei-Gorzo, O., Lassen, P. B., Darlay, R., Peltier, J., Palmer, J. M., Younes, R., Tiniakos, D., Aithal, G. P., Allison, M., Vacca, M., Goransson, M., Berlinguer-Palmini, R., … Hartlova, A. (2022). Macrophage scavenger receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease. Journal of Hepatology, 76(5), 1001-1012.
Guilliams, M., Bonnardel, J., Haest, B., Vanderborght, B., Wagner, C., Remmerie, A., Bujko, A., Martens, L., Thone, T., Browaeys, R., De Ponti, F. F., Vanneste, B., Zwicker, C., Svedberg, F. R., Vanhalewyn, T., Goncalves, A., Lippens, S., Devriendt, B., Cox, E., … Scott, C. L. (2022). Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches. Cell, 185(2), 379-396.e8.
Heymann, F., Hammerich, L., Storch, D., Bartneck, M., Huss, S., Russeler, V., Gassler, N., Lira, S. A., Luedde, T., Trautwein, C., & Tacke, F. (2012). Hepatic macrophage migration and differentiation critical for liver fibrosis is mediated by the chemokine receptor C-C motif chemokine receptor 8 in mice. Hepatology, 55(3), 898-909.
Heymann, F., Peusquens, J., Ludwig-Portugall, I., Kohlhepp, M., Ergen, C., Niemietz, P., Martin, C., van Rooijen, N., Ochando, J. C., Randolph, G. J., Luedde, T., Ginhoux, F., Kurts, C., Trautwein, C., & Tacke, F. (2015). Liver inflammation abrogates immunological tolerance induced by Kupffer cells. Hepatology, 62(1), 279-291.
Hou, J., Zhang, J., Cui, P., Zhou, Y., Liu, C., Wu, X., Ji, Y., Wang, S., Cheng, B., Ye, H., Shu, L., Zhang, K., Wang, D., Xu, J., Shu, Q., Colonna, M., & Fang, X. (2021). TREM2 sustains macrophage-hepatocyte metabolic coordination in nonalcoholic fatty liver disease and sepsis. The Journal of Clinical Investigation, 131(4), e135197.
Huang, W., Metlakunta, A., Dedousis, N., Zhang, P., Sipula, I., Dube, J. J., Scott, D. K., & O'Doherty, R. M. (2010). Depletion of liver Kupffer cells prevents the development of diet-induced hepatic steatosis and insulin resistance. Diabetes, 59(2), 347-357.
Ioannou, G. N. (2016). The role of cholesterol in the pathogenesis of NASH. Trends in Endocrinology and Metabolism, 27(2), 84-95.
Ioannou, G. N., Haigh, W. G., Thorning, D., & Savard, C. (2013). Hepatic cholesterol crystals and crown-like structures distinguish NASH from simple steatosis. Journal of Lipid Research, 54(5), 1326-1334.
Ioannou, G. N., Subramanian, S., Chait, A., Haigh, W. G., Yeh, M. M., Farrell, G. C., Lee, S. P., & Savard, C. (2017). Cholesterol crystallization within hepatocyte lipid droplets and its role in murine NASH. Journal of Lipid Research, 58(6), 1067-1079.
Jaitin, D. A., Adlung, L., Thaiss, C. A., Weiner, A., Li, B., Descamps, H., Lundgren, P., Bleriot, C., Liu, Z., Deczkowska, A., Keren-Shaul, H., David, E., Zmora, N., Eldar, S. M., Lubezky, N., Shibolet, O., Hill, D. A., Lazar, M. A., Colonna, M., … Amit, I. (2019). Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent manner. Cell, 178(3), 686-698.e4.
Jiang, Y., Tang, Y., Hoover, C., Kondo, Y., Huang, D., Restagno, D., Shao, B., Gao, L., Michael McDaniel, J., Zhou, M., Silasi-Mansat, R., McGee, S., Jiang, M., Bai, X., Lupu, F., Ruan, C., Marth, J. D., Wu, D., Han, Y., & Xia, L. (2021). Kupffer cell receptor CLEC4F is important for the destruction of desialylated platelets in mice. Cell Death and Differentiation, 28(11), 3009-3021.
Kim, S. Y., Jeong, J. M., Kim, S. J., Seo, W., Kim, M. H., Choi, W. M., Yoo, W., Lee, J. H., Shim, Y. R., Yi, H. S., Lee, Y. S., Eun, H. S., Lee, B. S., Chun, K., Kang, S. J., Kim, S. C., Gao, B., Kunos, G., Kim, H. M., & Jeong, W. I. (2017). Pro-inflammatory hepatic macrophages generate ROS through NADPH oxidase 2 via endocytosis of monomeric TLR4-MD2 complex. Nature Communications, 8(1), 2247.
Kourtzelis, I., Hajishengallis, G., & Chavakis, T. (2020). Phagocytosis of apoptotic cells in resolution of inflammation. Frontiers in Immunology, 11, 553.
Krenkel, O., Hundertmark, J., Abdallah, A. T., Kohlhepp, M., Puengel, T., Roth, T., Branco, D. P. P., Mossanen, J. C., Luedde, T., Trautwein, C., Costa, I. G., & Tacke, F. (2020). Myeloid cells in liver and bone marrow acquire a functionally distinct inflammatory phenotype during obesity-related steatohepatitis. Gut, 69(3), 551-563.
Krenkel, O., Puengel, T., Govaere, O., Abdallah, A. T., Mossanen, J. C., Kohlhepp, M., Liepelt, A., Lefebvre, E., Luedde, T., Hellerbrand, C., Weiskirchen, R., Longerich, T., Costa, I. G., Anstee, Q. M., Trautwein, C., & Tacke, F. (2018). Therapeutic inhibition of inflammatory monocyte recruitment reduces steatohepatitis and liver fibrosis. Hepatology, 67(4), 1270-1283.
Krenkel, O., & Tacke, F. (2017). Liver macrophages in tissue homeostasis and disease. Nature Reviews Immunology, 17(5), 306-321.
Lancaster, G. I., Langley, K. G., Berglund, N. A., Kammoun, H. L., Reibe, S., Estevez, E., Weir, J., Mellett, N. A., Pernes, G., Conway, J. R. W., Lee, M. K. S., Timpson, P., Murphy, A. J., Masters, S. L., Gerondakis, S., Bartonicek, N., Kaczorowski, D. C., Dinger, M. E., Meikle, P. J., … Febbraio, M. A. (2018). Evidence that TLR4 is not a receptor for saturated fatty acids but mediates Lipid-induced inflammation by reprogramming macrophage metabolism. Cell Metabolism, 27, 1096-1110 e1095.
Leroux, A., Ferrere, G., Godie, V., Cailleux, F., Renoud, M. L., Gaudin, F., Naveau, S., Prevot, S., Makhzami, S., Perlemuter, G., & Cassard-Doulcier, A. M. (2012). Toxic lipids stored by Kupffer cells correlates with their pro-inflammatory phenotype at an early stage of steatohepatitis. Journal of Hepatology, 57(1), 141-149.
Luo, X., Li, H., Ma, L., Zhou, J., Guo, X., Woo, S. L., Pei, Y., Knight, L. R., Deveau, M., Chen, Y., Qian, X., Xiao, X., Li, Q., Chen, X., Huo, Y., McDaniel, K., Francis, H., Glaser, S., Meng, F., … Wu, C. (2018). Expression of STING is increased in liver tissues from patients with NAFLD and promotes macrophage-mediated hepatic inflammation and fibrosis in mice. Gastroenterology, 155(6), 1971-1984.e4.
Luo, Z., Ji, Y., Gao, H., Gomes Dos Reis, F. C., Bandyopadhyay, G., Jin, Z., Ly, C., Chang, Y. J., Zhang, D., Kumar, D., & Ying, W. (2021). CRIg(+) macrophages prevent gut microbial DNA-containing extracellular vesicle-induced tissue inflammation and insulin resistance. Gastroenterology, 160(3) 863-874.
MacParland, S. A., Liu, J. C., Ma, X. Z., Innes, B. T., Bartczak, A. M., Gage, B. K., Manuel, J., Khuu, N., Echeverri, J., Linares, I., Gupta, R., Cheng, M. L., Liu, L. Y., Camat, D., Chung, S. W., Seliga, R. K., Shao, Z., Lee, E., Ogawa, S., … McGilvray, I. D. (2018). Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations. Nature Communications, 9(1), 4383.
McGettigan, B., McMahan, R., Orlicky, D., Burchill, M., Danhorn, T., Francis, P., Cheng, L. L., Golden-Mason, L., Jakubzick, C. V., & Rosen, H. R. (2019). Dietary lipids differentially shape nonalcoholic steatohepatitis progression and the transcriptome of kupffer cells and infiltrating macrophages. Hepatology, 70(1), 67-83.
Miura, K., Yang, L., van Rooijen, N., Ohnishi, H., & Seki, E. (2012). Hepatic recruitment of macrophages promotes nonalcoholic steatohepatitis through CCR2. American Journal of Physiology. Gastrointestinal and Liver Physiology, 302(11), G1310-G1321.
Mridha, A. R., Wree, A., Robertson, A. A. B., Yeh, M. M., Johnson, C. D., Van Rooyen, D. M., Haczeyni, F., Teoh, N. C., Savard, C., Ioannou, G. N., Masters, S. L., Schroder, K., Cooper, M. A., Feldstein, A. E., & Farrell, G. C. (2017). NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice. Journal of Hepatology, 66(5), 1037-1046.
Nati, M., Chung, K. J., & Chavakis, T. (2022). The role of innate immune cells in nonalcoholic fatty liver disease. Journal of Innate Immunity, 14(1), 31-41.
Papachristoforou, E., & Ramachandran, P. (2022). Macrophages as key regulators of liver health and disease. International Review of Cell and Molecular Biology, 368, 143-212.
Pradere, J. P., Kluwe, J., De Minicis, S., Jiao, J. J., Gwak, G. Y., Dapito, D. H., Jang, M. K., Guenther, N. D., Mederacke, I., Friedman, R., Dragomir, A. C., Aloman, C., & Schwabe, R. F. (2013). Hepatic macrophages but not dendritic cells contribute to liver fibrosis by promoting the survival of activated hepatic stellate cells in mice. Hepatology, 58, 1461-1473.
Ramachandran, P., Dobie, R., Wilson-Kanamori, J. R., Dora, E. F., Henderson, B. E. P., Luu, N. T., Portman, J. R., Matchett, K. P., Brice, M., Marwick, J. A., Taylor, R. S., Efremova, M., Vento-Tormo, R., Carragher, N. O., Kendall, T. J., Fallowfield, J. A., Harrison, E. M., Mole, D. J., Wigmore, S. J., … Henderson N. C. (2019). Resolving the fibrotic niche of human liver cirrhosis at single-cell level. Nature, 575(7783), 512-518.
Ratziu, V., Sanyal, A., Harrison, S. A., Wong, V. W., Francque, S., Goodman, Z., Aithal, G. P., Kowdley, K. V., Seyedkazemi, S., Fischer, L., Loomba, R., Abdelmalek, M. F., & Tacke, F. (2020). Cenicriviroc treatment for adults with nonalcoholic steatohepatitis and fibrosis: Final analysis of the phase 2b CENTAUR study. Hepatology, 72(3), 892-905.
Reid, D. T., Reyes, J. L., McDonald, B. A., Vo, T., Reimer, R. A., & Eksteen, B. (2016). Kupffer cells undergo fundamental changes during the development of experimental NASH and are critical in initiating liver damage and inflammation. PLoS ONE, 11(7), e0159524.
Remmerie, A., Martens, L., Thone, T., Castoldi, A., Seurinck, R., Pavie, B., Roels, J., Vanneste, B., De Prijck, S., Vanhockerhout, M., Binte Abdul Latib, M., Devisscher, L., Hoorens, A., Bonnardel, J., Vandamme, N., Kremer, A., Borghgraef, P., Van Vlierberghe, H., Lippens, S., … Scott C. L. (2020). Osteopontin expression identifies a subset of recruited macrophages distinct from kupffer cells in the fatty liver. Immunity, 53(3), 641-657.e4.
Scott, C. L., & Guilliams, M. (2018). The role of Kupffer cells in hepatic iron and lipid metabolism. Journal of Hepatology, 69(5), 1197-1199.
Scott, C. L., T'Jonck, W., Martens, L., Todorov, H., Sichien, D., Soen, B., Bonnardel, J., De Prijck, S., Vandamme, N., Cannoodt, R., Saelens, W., Vanneste, B., Toussaint, W., De Bleser, P., Takahashi, N., Vandenabeele, P., Henri, S., Pridans, C., Hume, D. A., … Guilliams M. (2018). The transcription factor ZEB2 is required to maintain the Tissue-specific identities of macrophages. Immunity, 49(2), 312-325.e5.
Scott, C. L., Zheng, F., De Baetselier, P., Martens, L., Saeys, Y., De Prijck, S., Lippens, S., Abels, C., Schoonooghe, S., Raes, G., Devoogdt, N., Lambrecht, B. N., Beschin, A., & Guilliams, M. (2016). Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells. Nature Communications, 7, 10321.
Seidman, J. S., Troutman, T. D., Sakai, M., Gola, A., Spann, N. J., Bennett, H., Bruni, C. M., Ouyang, Z., Li, R. Z., Sun, X., Vu, B. T., Pasillas, M. P., Ego, K. M., Gosselin, D., Link, V. M., Chong, L. W., Evans, R. M., Thompson, B. M., McDonald, J. G., … Glass, C. K. (2020). Niche-specific reprogramming of epigenetic landscapes drives myeloid cell diversity in nonalcoholic steatohepatitis. Immunity, 52(6), 1057-1074.e7.
Sierro, F., Evrard, M., Rizzetto, S., Melino, M., Mitchell, A. J., Florido, M., Beattie, L., Walters, S. B., Tay, S. S., Lu, B., Holz, L. E., Roediger, B., Wong, Y. C., Warren, A., Ritchie, W., McGuffog, C., Weninger, W., Le Couteur, D. G., Ginhoux, F., … Bertolino P. (2017). A liver capsular network of Monocyte-derived macrophages restricts hepatic dissemination of intraperitoneal bacteria by neutrophil recruitment. Immunity, 47(2), 374-388 e376.
Soucie, E. L., Weng, Z., Geirsdottir, L., Molawi, K., Maurizio, J., Fenouil, R., Mossadegh-Keller, N., Gimenez, G., VanHille, L., Beniazza, M., Favret, J., Berruyer, C., Perrin, P., Hacohen, N., Andrau, J. C., Ferrier, P., Dubreuil, P., Sidow, A., & Sieweke, M. H. (2016). Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells. Science, 351(6274), aad5510.
Stienstra, R., Saudale, F., Duval, C., Keshtkar, S., Groener, J. E., van Rooijen, N., Staels, B., Kersten, S., & Muller, M. (2010). Kupffer cells promote hepatic steatosis via interleukin-1beta-dependent suppression of peroxisome proliferator-activated receptor alpha activity. Hepatology, 51(2), 511-522.
Subramanian, P., Hampe, J., Tacke, F., & Chavakis, T. (2022). Fibrogenic pathways in metabolic dysfunction associated fatty liver disease (MAFLD). International Journal of Molecular Sciences, 23(13), 6996.
Terpstra, V., & van Berkel, T. J. (2000). Scavenger receptors on liver Kupffer cells mediate the in vivo uptake of oxidatively damaged red blood cells in mice. Blood, 95(6), 2157-2163.
Thibaut, R., Gage, M. C., Pineda-Torra, I., Chabrier, G., Venteclef, N., & Alzaid, F. (2022). Liver macrophages and inflammation in physiology and physiopathology of non-alcoholic fatty liver disease. Febs Journal, 289(11), 3024-3057.
Tosello-Trampont, A. C., Landes, S. G., Nguyen, V., Novobrantseva, T. I., & Hahn, Y. S. (2012). Kuppfer cells trigger nonalcoholic steatohepatitis development in diet-induced mouse model through tumor necrosis factor-alpha production. Journal of Biological Chemistry, 287(48), 40161-40172.
Traber, P. G., Chou, H., Zomer, E., Hong, F., Klyosov, A., Fiel, M. I., & Friedman, S. L. (2013). Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors in thioacetamide-induced liver disease. PLoS ONE, 8(10), e75361.
Tran, S., Baba, I., Poupel, L., Dussaud, S., Moreau, M., Gelineau, A., Marcelin, G., Magreau-Davy, E., Ouhachi, M., Lesnik, P., Boissonnas, A., Le Goff, W., Clausen, B. E., Yvan-Charvet, L., Sennlaub, F., Huby, T., & Gautier, E. L. (2020). Impaired kupffer cell self-renewal alters the liver response to lipid overload during non-alcoholic steatohepatitis. Immunity, 53(3), 627-640.e5.
Vilar-Gomez, E., Calzadilla-Bertot, L., Wai-Sun Wong, V., Castellanos, M., Aller-de la Fuente, R., Metwally, M., Eslam, M., Gonzalez-Fabian, L., Alvarez-Quinones Sanz, M., Conde-Martin, A. F., De Boer, B., McLeod, D., Hung Chan, A. W., Chalasani, N., George, J., Adams, L. A., & Romero-Gomez, M. (2018). Fibrosis severity as a determinant of cause-specific mortality in patients with advanced nonalcoholic fatty liver disease: A multi-national cohort study. Gastroenterology, 155(2), 443-457.e7.
Wang, X., de Carvalho Ribeiro, M., Iracheta-Vellve, A., Lowe, P., Ambade, A., Satishchandran, A., Bukong, T., Catalano, D., Kodys, K., & Szabo, G. (2019). Macrophage-Specific Hypoxia-Inducible Factor-1alpha contributes to impaired autophagic flux in nonalcoholic steatohepatitis. Hepatology, 69(2), 545-563.
Wang, Y., van der Tuin, S., Tjeerdema, N., van Dam, A. D., Rensen, S. S., Hendrikx, T., Berbee, J. F., Atanasovska, B., Fu, J., Hoekstra, M., Bekkering, S., Riksen, N. P., Buurman, W. A., Greve, J. W., Hofker, M. H., Shiri-Sverdlov, R., Meijer, O. C., Smit, J. W., Havekes, L. M., … Rensen, P. C. (2015). Plasma cholesteryl ester transfer protein is predominantly derived from Kupffer cells. Hepatology, 62(6), 1710-1722.
Wen, Y., Lambrecht, J., Ju, C., & Tacke, F. (2021). Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities. Cellular & Molecular Immunology, 18(1), 45-56.
Willekens, F. L., Werre, J. M., Kruijt, J. K., Roerdinkholder-Stoelwinder, B., Groenen-Dopp, Y. A., van den Bos, A. G., Bosman, G. J., & van Berkel, T. J. (2005). Liver Kupffer cells rapidly remove red blood cell-derived vesicles from the circulation by scavenger receptors. Blood, 105(5), 2141-2145.
Xiong, X., Kuang, H., Ansari, S., Liu, T., Gong, J., Wang, S., Zhao, X. Y., Ji, Y., Li, C., Guo, L., Zhou, L., Chen, Z., Leon-Mimila, P., Chung, M. T., Kurabayashi, K., Opp, J., Campos-Perez, F., Villamil-Ramirez, H., Canizales-Quinteros, S., … Lin J. D. (2019). Landscape of intercellular crosstalk in healthy and NASH liver revealed by Single-cell secretome gene analysis. Molecular Cell, 75(3), 644-660e5.
Xu, L., Liu, W., Bai, F., Xu, Y., Liang, X., Ma, C., & Gao, L. (2021). Hepatic macrophage as a key player in fatty liver disease. Frontiers in Immunology, 12, 708978.
You, Q., Cheng, L., Kedl, R. M., & Ju, C. (2008). Mechanism of T cell tolerance induction by murine hepatic Kupffer cells. Hepatology, 48(3), 978-990.
Younossi, Z., Anstee, Q. M., Marietti, M., Hardy, T., Henry, L., Eslam, M., George, J., & Bugianesi, E. (2018). Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nature reviews Gastroenterology & Hepatology, 15(1), 11-20.
Younossi, Z. M., Blissett, D., Blissett, R., Henry, L., Stepanova, M., Younossi, Y., Racila, A., Hunt, S., & Beckerman, R. (2016a). The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology, 64(5), 1577-1586.
Younossi, Z. M., Koenig, A. B., Abdelatif, D., Fazel, Y., Henry, L., & Wymer, M. (2016b). Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology, 64(1), 73-84.
Zeng, Z., Surewaard, B. G., Wong, C. H., Geoghegan, J. A., Jenne, C. N., & Kubes, P. (2016). CRIg functions as a macrophage pattern recognition receptor to directly bind and capture Blood-borne gram-positive bacteria. Cell Host and Microbe, 20(1), 99-106.