Dendritic Cells Limit Fibroinflammatory Injury in Nonalcoholic Steatohepatitis in Mice
Open accessAbstract
Nonalcoholic steatohepatitis (NASH) is the most common etiology of chronic liver dysfunction in the United States and can progress to cirrhosis and liver failure. Inflammatory insult resulting from fatty infiltration of the liver is central to disease pathogenesis. Dendritic cells (DCs) are antigen-presenting cells with an emerging role in hepatic inflammation. We postulated that DCs are important in the progression of NASH. We found that intrahepatic DCs expand and mature in NASH liver and assume an activated immune phenotype. However, rather than mitigating the severity of NASH, DC depletion markedly exacerbated intrahepatic fibroinflammation. Our mechanistic studies support a regulatory role for DCs in NASH by limiting sterile inflammation through their role in the clearance of apoptotic cells and necrotic debris. We found that DCs limit CD8+ T-cell expansion and restrict Toll-like receptor expression and cytokine production in innate immune effector cells in NASH, including Kupffer cells, neutrophils, and inflammatory monocytes. Consistent with their regulatory role in NASH, during the recovery phase of disease, ablation of DC populations results in delayed resolution of intrahepatic inflammation and fibroplasia. Conclusion : Our findings support a role for DCs in modulating NASH. Targeting DC functional properties may hold promise for therapeutic intervention in NASH. (HEPATOLOGY 2013;58:589–602)
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Activated dendritic cells increase in abundance in NASH and coordinate the adaptive immune response as professional antigen presenting cells.
“Activated dendritic cells (DCs) increase in abundance, coordinating the adaptive immune response as professional antigen presenting cells (APCs) (18).”
From Hepatic Stellate Cell-Immune Interactions in NASH (2022) · cites this paper as [18]
The NASH T cell response is characterized by an enrichment for cytotoxic CD8+ T, TH1 differentiated CD4+ T and NKT cell populations.
“The NASH T cell response is characterized by an enrichment for cytotoxic CD8+ T, TH1 differentiated CD4+ T and NKT cell populations (18, 121, 131–135).”
From Hepatic Stellate Cell-Immune Interactions in NASH (2022) · cites this paper as [18]
These immune shifts drive hepatocyte metabolic dysregulation through IFNγ, TNFα, and IL-17A signaling and production of the lymphotoxin LIGHT.
“These immune shifts drive hepatocyte metabolic dysregulation through IFNγ, TNFα, and IL-17A signaling and production of the lymphotoxin LIGHT (18, 121, 132, 133).”
From Hepatic Stellate Cell-Immune Interactions in NASH (2022) · cites this paper as [18]
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Sterile inflammation: sensing and reacting to damage
Chen, G. Y., & Nuñez, G. (2010) · Nature Reviews Immunology · doi:10.1038/nri2873 · Cited by 3,051 · see citing works
Nishimura, S., Manabe, I., Nagasaki, M., Eto, K., Yamashita, H., Ohsugi, M., Otsu, M., Hara, K., Ueki, K., Sugiura, S., et al. (2009) · Nature Medicine · doi:10.1038/nm.1964 · Cited by 2,230 · see citing works
Powell, E. E., Cooksley, G. W. E., Hanson, R., Searle, J., Halliday, J. W., & Powell, L. W. (1990) · Hepatology · doi:10.1002/hep.1840110114 · Cited by 1,473 · see citing works
Mofrad, P., Contos, M., Haque, M., Sargeant, C. C., Fisher, R., Luketic, V., Sterling, R., Shiffman, M., Stravitz, R., & Sanyal, A. (2003) · Hepatology · doi:10.1053/jhep.2003.50229 · Cited by 1,221 · see citing works
Akbari, O., DeKruyff, R. H., & Umetsu, D. T. (2001) · Nature Immunology · doi:10.1038/90667 · Cited by 1,196 · see citing works
Younossi, Z. M., Stepanova, M., Afendy, M., Fang, Y. H., Younossi, Y., Mir, H., & Srishord, M. K. (2011) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2011.03.020 · Cited by 1,072 · see citing works
Identification of a dendritic cell receptor that couples sensing of necrosis to immunity
Sancho, D., Joffre, O. P., Keller, A. M., Rogers, N. C., Martínez, D., Hernanz-Falcón, P., Rosewell, I., & Sousa, C. R. E. (2009) · Nature · doi:10.1038/nature07750 · Cited by 750 · see citing works
Toll-Like Receptor 9 Promotes Steatohepatitis by Induction of Interleukin-1β in Mice
Miura, K., Kodama, Y., Inokuchi, S., Schnabl, B., Aoyama, T., Ohnishi, H., Olefsky, J. M., Brenner, D. A., & Seki, E. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.03.052 · Cited by 741 · see citing works
Toll‐like receptors and adaptor molecules in liver disease: Update†
Seki, E., & Brenner, D. A. (2008) · Hepatology · doi:10.1002/hep.22306 · Cited by 722 · see citing works
Rivera, C. A., Adegboyega, P., van Rooijen, N., Tagalicud, A., Allman, M., & Wallace, M. (2007) · Journal of Hepatology · doi:10.1016/j.jhep.2007.04.019 · Cited by 693 · see citing works
Marrero, J., Fontana, R. J., Su, G. L., Conjeevaram, H. S., Emick, D. M., & Lok, A. S.-F. (2002) · Hepatology · doi:10.1053/jhep.2002.36939 · Cited by 659 · see citing works
Tomita, K., Tamiya, G., Ando, S., Ohsumi, K., Chiyo, T., Mizutani, A., Kitamura, N., Toda, K., Kaneko, T., Horie, Y., et al. (2005) · Gut · doi:10.1136/gut.2005.071118 · Cited by 439 · see citing works
The Dendritic Cell Receptor Clec9A Binds Damaged Cells via Exposed Actin Filaments
Zhang, J., Czabotar, P. E., Policheni, A. N., Caminschi, I., Wan, S. S., Kitsoulis, S., Tullett, K. M., Robin, A. Y., Brammananth, R., van Delft, M. F., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.03.009 · Cited by 342 · see citing works
Rovere, P. Q., Peri, G., Fazzini, F., Bottazzi, B., Doni, A., Bondanza, A., Zimmermann, V. S., Garlanda, C., Fascio, U., Sabbadini, M. G., et al. (2000) · Blood · doi:10.1182/blood.v96.13.4300 · Cited by 326 · see citing works
Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis
Guo, J., & Friedman, S. L. (2010) · Fibrogenesis & Tissue Repair · doi:10.1186/1755-1536-3-21 · Cited by 315 · see citing works
Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease
Tang, Y., Bian, Z., Zhao, L., Liu, Y., Liang, S., Wang, Q., Han, X., Peng, Y., Chen, X., Shen, L., et al. (2011) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2011.04471.x · Cited by 294 · see citing works
Increased Hepatic Myeloperoxidase Activity in Obese Subjects with Nonalcoholic Steatohepatitis
Rensen, S. S., Slaats, Y., Nijhuis, J., Jans, A., Bieghs, V., Driessen, A., Malle, E., Greve, J. W., & Buurman, W. A. (2009) · The American Journal of Pathology · doi:10.2353/ajpath.2009.080999 · Cited by 290 · see citing works
In liver fibrosis, dendritic cells govern hepatic inflammation in mice via TNF-α
Connolly, M. K., Bedrosian, A. S., Clair, J. M., Mitchell, A. P., Ibrahim, J., Stroud, A., Pachter, H. L., Bar‐Sagi, D., Frey, A. B., & Miller, G. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37581 · Cited by 266 · see citing works
Self-citationAlkhouri, N., Morris‐Stiff, G., Campbell, C., Lopez, R., Tamimi, T. A., Yerian, L., Zein, N. N., & Feldstein, A. E. (2012) · Liver International · doi:10.1111/j.1478-3231.2011.02639.x · Cited by 256 · see citing works
Li, L., Chen, L., Hu, L., Liu, Y., Sun, H., Tang, J. P., Hou, Y.-J., Chang, Y., Tu, Q., Feng, G., et al. (2011) · Hepatology · doi:10.1002/hep.24552 · Cited by 236 · see citing works
A high-fat diet and regulatory T cells influence susceptibility to endotoxin-induced liver injury
Ma, X., Hua, J., Mohamood, A. R., Hamad, A. R. A., Ravi, R. K., & Li, Z. (2007) · Hepatology · doi:10.1002/hep.21823 · Cited by 199 · see citing works
Conventional DCs reduce liver ischemia/reperfusion injury in mice via IL-10 secretion
Bamboat, Z. M., Ocuin, L. M., Balachandran, V. P., Obaid, H., Plitas, G., & DeMatteo, R. P. (2010) · Journal of Clinical Investigation · doi:10.1172/jci40008 · Cited by 183 · see citing works
Fishbein, M. H., Miner, M., Mogren, C., & Chalekson, J. (2003) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/00005176-200301000-00012 · Cited by 179 · see citing works
Dendritic Cell Regulation of Carbon Tetrachloride–Induced Murine Liver Fibrosis Regression
Jiao, J., Sastre, D., Fiel, M. I., Lee, U. E., Ghiassi–Nejad, Z., Ginhoux, F., Vivier, E., Friedman, S. L., Merad, M., & Aloman, C. (2012) · Hepatology · doi:10.1002/hep.24621 · Cited by 154 · see citing works
Functionally relevant neutrophilia in CD11c diphtheria toxin receptor transgenic mice
Tittel, A. P., Heuser-Loy, C., Ohliger, C., Llanto, C., Yona, S., Hämmerling, G. J., Engel, D. R., Garbi, N., & Kurts, C. (2012) · Nature Methods · doi:10.1038/nmeth.1905 · Cited by 143 · see citing works
Apoptosis in experimental NASH is associated with p53 activation and TRAIL receptor expression
Farrell, G. C., Larter, C. Z., Hou, J. Y., Zhang, R. H., Yeh, M. M., Williams, J., Peňa, A. D., Francisco, R., Osvath, S. R., Brooling, J. T., et al. (2009) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2009.05785.x · Cited by 137 · see citing works
Afzali, A., Berry, K., & Ioannou, G. N. (2011) · Liver Transplantation · doi:10.1002/lt.22435 · Cited by 135 · see citing works
Fei, M., Bhatia, S., Oriss, T. B., Yarlagadda, M., Khare, A., Akira, S., Saijo, S., Iwakura, Y., Fallert Junecko, B. A., Reinhart, T. A., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1015476108 · Cited by 127 · see citing works
Apoptosis and Cytokines in Non-Alcoholic Steatohepatitis
Syn, W., Choi, S. S., & Diehl, A. M. (2009) · Clinics in Liver Disease · doi:10.1016/j.cld.2009.07.003 · Cited by 124 · see citing works
Bechmann, L. P., Gieseler, R. K. H., Sowa, J., Kahraman, A., ERHARD, J., Wedemeyer, I., Emons, B., Jochum, C., Feldkamp, T., Gerken, G., et al. (2009) · Liver International · doi:10.1111/j.1478-3231.2010.02248.x · Cited by 120 · see citing works
Miller, G., Lahrs, S., Pillarisetty, V. G., Shah, A. B., & DeMatteo, R. P. (2002) · PubMed · Cited by 107 · see citing works
Self-citationEndogenous IL-10 Attenuates Cisplatin Nephrotoxicity: Role of Dendritic Cells
Tadagavadi, R. K., & Reeves, W. B. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1000383 · Cited by 102 · see citing works
Hepatic dendritic cell subsets in the mouse
Jomantaitė, I., Dikopoulos, N., Kröger, A., Leithäuser, F., Hauser, H., Schirmbeck, R., & Reimann, J. (2004) · European Journal of Immunology · doi:10.1002/eji.200324336 · Cited by 92 · see citing works
Dendritic cell depletion exacerbates acetaminophen hepatotoxicity
Connolly, M. K., Ayo, D., Malhotra, A., Hackman, M., Bedrosian, A. S., Ibrahim, J., Cieza-Rubio, N. E., Nguyen, A. H., Henning, J. R., Dorvil-Castro, M., et al. (2011) · Hepatology · doi:10.1002/hep.24429 · Cited by 90 · see citing works
Self-citationA Role for Dendritic Cells in Bleomycin-induced Pulmonary Fibrosis in Mice?
Bantsimba-Malanda, C., Marchal-Sommé, J., Goven, D., Freynet, O., Michel, L., Crestani, B., & Soler, P. (2010) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200907-1164oc · Cited by 86 · see citing works
Role of mucosal dendritic cells in inflammatory bowel disease
Niess, J. H. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.14.5138 · Cited by 82 · see citing works
Katz, S. C., Ryan, K., Ahmed, N., Plitas, G., Chaudhry, U. I., Kingham, T. P., Naheed, S., Nguyen, C., Somasundar, P., Espat, N. J., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1004077 · Cited by 79 · see citing works
Dendritic Cells Promote Pancreatic Viability in Mice With Acute Pancreatitis
Bedrosian, A. S., Nguyen, A. H., Hackman, M., Connolly, M. K., Malhotra, A., Ibrahim, J., Cieza-Rubio, N. E., Henning, J. R., Barilla, R., Rehman, A. U., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.07.033 · Cited by 66 · see citing works
Self-citationRole of mucosal dendritic cells in inflammatory bowel disease
Jan, Hendrik, H., & Niess (2008) · Acta Scientiarum Naturalium Universitatis Sunyatseni · Cited by 64 · see citing works
Depletion of Macrophages and Dendritic Cells in Ischemic Acute Kidney Injury
Lu, L., Faubel, S. G., He, Z., Andrés-Hernando, A., Jani, A. H., Kedl, R. M., & Edelstein, C. L. (2012) · American Journal of Nephrology · doi:10.1159/000335582 · Cited by 59 · see citing works
Venet, F., Huang, X., Chung, C., Chen, Y., & Ayala, A. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2010.090765 · Cited by 51 · see citing works
CD8+ T cells drive adipose tissue inflammation – A novel clue for NASH pathogenesis?
Popov, Y. V., & Schuppan, D. (2009) · Journal of Hepatology · doi:10.1016/j.jhep.2009.10.019 · Cited by 17 · see citing works
Flagged first, then by citations
1 of the 43 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- [31]Nishimura S Manabe I Nagasaki M CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity Nat Med 2009 15 914 920 19633658
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Immunology in the liver — from homeostasis to disease
Heymann, F., & Tacke, F. (2016) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2015.200 · Cited by 1,180 · see citing works
The immunology of hepatocellular carcinoma
Ringelhan, M., Pfister, D., O’Connor, T., Pikarsky, E., & Heikenwalder, M. (2018) · Nature Immunology · doi:10.1038/s41590-018-0044-z · Cited by 1,076 · see citing works
Hepatic inflammatory responses in liver fibrosis
Hammerich, L., & Tacke, F. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00807-x · Cited by 803 · see citing works
NAFLD causes selective CD4+ T lymphocyte loss and promotes hepatocarcinogenesis
Ma, C., Kesarwala, A. H., Eggert, T., Medina-Echeverz, J., Kleiner, D. E., Jin, P., Stroncek, D. F., Terabe, M., Kapoor, V., ElGindi, M., et al. (2016) · Nature · doi:10.1038/nature16969 · Cited by 766 · see citing works
Peiseler, M., Schwabe, R., Hampe, J., Kubes, P., Heikenwälder, M., & Tacke, F. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.06.012 · Cited by 564 · see citing works
Non-alcoholic fatty liver disease: the interplay between metabolism, microbes and immunity
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Dendritic Cell Paucity Leads to Dysfunctional Immune Surveillance in Pancreatic Cancer
Hegde, S., Lander, V. E., Herzog, B. H., Zuo, C., Breden, M. A., Knolhoff, B. L., Hogg, G. D., Tang, J. P., Baer, J. M., Mpoy, C., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.02.008 · Cited by 454 · see citing works
Adaptive immunity: an emerging player in the progression of NAFLD
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Nonalcoholic fatty liver disease in adults: current concepts in etiology, outcomes, and management
Marjot, T., Moolla, A., Cobbold, J. F., Hodson, L., & Tomlinson, J. W. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnz009 · Cited by 228 · see citing works
Immunological mechanisms and therapeutic targets of fatty liver diseases
Wang, H., Mehal, W. Z., Nagy, L. E., & Rotman, Y. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-00579-3 · Cited by 222 · see citing works
Liver fibrosis in NAFLD/NASH: from pathophysiology towards diagnostic and therapeutic strategies
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Cellular mechanisms of tissue fibrosis. 5. Novel insights into liver fibrosis
Mallat, A., & Lotersztajn, S. (2013) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00230.2013 · Cited by 211 · see citing works
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The Role of Innate Immune Cells in Nonalcoholic Steatohepatitis
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XCR1+ type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis
Deczkowska, A., David, E., Ramadori, P., Pfister, D., Safran, M., Li, B., Giladi, A., Jaitin, D. A., Barboy, O., Cohen, M., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01344-3 · Cited by 197 · see citing works
Death Receptor-Mediated Cell Death and Proinflammatory Signaling in Nonalcoholic Steatohepatitis
Hirsova, P., & Gores, G. (2014) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2014.11.005 · Cited by 184 · see citing works
Type I Interferon Responses Drive Intrahepatic T Cells to Promote Metabolic Syndrome
Ghazarian, M., Revelo, X. S., Nøhr, M. K., Luck, H., Zeng, K., Lei, H., Tsai, S., Schroer, S. A., Park, Y. J., Chng, M. H. Y., et al. (2017) · Science Immunology · doi:10.1126/sciimmunol.aai7616 · Cited by 190 · see citing works
Immune and inflammatory pathways in NASH
Ganz, M., & Szabó, G. (2013) · Hepatology International · doi:10.1007/s12072-013-9468-6 · Cited by 188 · see citing works
Haas, J. T., Vonghia, L., Mogilenko, D. A., Verrijken, A., Molendi-Coste, O., Fleury, S., Deprince, A., Nikitin, A., Woitrain, E., Ducrocq-Geoffroy, L., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0076-1 · Cited by 155 · see citing works
Vitamin D: A new player in non-alcoholic fatty liver disease?
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Hepatic lipid metabolism and non-alcoholic fatty liver disease in aging
Gong, Z., Tas, E., Yakar, S., & Muzumdar, R. H. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.12.022 · Cited by 147 · see citing works
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Tosello‐Trampont, A., Krueger, P., Narayanan, S., Landes, S. G., Leitinger, N., & Hahn, Y. S. (2016) · Hepatology · doi:10.1002/hep.28389 · Cited by 142 · see citing works
The bidirectional immune crosstalk in metabolic dysfunction-associated steatotic liver disease
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Handa, P., Morgan‐Stevenson, V., Maliken, B. D., Nelson, J. E., Washington, S., Westerman, M. E., Yeh, M. M., & Kowdley, K. V. (2015) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00246.2015 · Cited by 132 · see citing works
Nati, M., Haddad, D., Birkenfeld, A. L., Koch, C. A., Chavakis, T., & Chatzigeorgiou, A. (2016) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-016-9339-2 · Cited by 132 · see citing works
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Tomita, K., Freeman, B. L., Bronk, S. F., LeBrasseur, N. K., White, T. A., Hirsova, P., & Ibrahim, S. H. (2016) · Scientific Reports · doi:10.1038/srep28786 · Cited by 128 · see citing works
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Magee, N. S., Zou, A., & Zhang, Y. (2016) · BioMed Research International · doi:10.1155/2016/5170402 · Cited by 108 · see citing works
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Eilam, Y., Khattib, H., Pintel, N., & Avni, D. (2023) · Global Challenges · doi:10.1002/gch2.202200177 · Cited by 101 · see citing works
Ono, Y., Pérez-Gutiérrez, A., Nakao, T., Dai, H., Camirand, G., Yoshida, O., Yokota, S., Stolz, D. B., Ross, M. A., Morelli, A. E., et al. (2017) · Hepatology · doi:10.1002/hep.29529 · Cited by 101 · see citing works
The pathophysiology of MASLD: an immunometabolic perspective
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Murine CD103+ dendritic cells protect against steatosis progression towards steatohepatitis
Heier, E.-C., Meier, A., Julich-Haertel, H., Djudjaj, S., Rau, M., Tschernig, T., Geier, A., Boor, P., Lammert, F., & Lukacs-Kornek, V. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.01.008 · Cited by 94 · see citing works
Autophagy: A Multifaceted Partner in Liver Fibrosis
Mallat, A., Lodder, J., Teixeira-Clerc, F., Moreau, R., Codogno, P., & Lotersztajn, S. (2014) · BioMed Research International · doi:10.1155/2014/869390 · Cited by 93 · see citing works
Orlicky, D. J., Libby, A. E., Bales, E. S., McMahan, R. H., Monks, J., Rosa, F. G. L., & McManaman, J. L. (2018) · The Journal of Physiology · doi:10.1113/jp277140 · Cited by 87 · see citing works
Eckert, C., Klein, N., Kornek, M., & Kornek, M. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00179 · Cited by 83 · see citing works
γδ T Cells Promote Steatohepatitis by Orchestrating Innate and Adaptive Immune Programming
Torres‐Hernandez, A., Wang, W., Nikiforov, Y., Tejada, K., Torres, L., Kalabin, A., Adam, S., Wu, J., Lu, L., Chen, R., et al. (2020) · Hepatology · doi:10.1002/hep.30952 · Cited by 80 · see citing works
Self-citationCX3CR1-expressing inflammatory dendritic cells contribute to the progression of steatohepatitis
Sutti, S., Locatelli, I., Bruzzì, S., Jindal, A., Vacchiano, M., Bozzola, C., & Albano, E. (2015) · Clinical Science · doi:10.1042/cs20150053 · Cited by 80 · see citing works
Hepatic Stellate Cell-Immune Interactions in NASH
Carter, J. K., & Friedman, S. L. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.867940 · Cited by 79 · see citing works
Wang, X., Hausding, M., Weng, S., Kim, Y. O., Steven, S., Klein, T., Daiber, A., & Schuppan, D. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6953 · Cited by 79 · see citing works
Dagorn, P. G., Foretz, M., Steinberg, G. R., Batchuluun, B., Zawistowska‐Deniziak, A., Lambooij, J. M., Guigas, B., Carling, D., Monternier, P., Moller, D. E., et al. (2021) · Hepatology Communications · doi:10.1002/hep4.1799 · Cited by 78 · see citing works
Krishnan, A., Abdullah, T. S., Mounajjed, T., Hartono, S. P., McConico, A. L., White, T., LeBrasseur, N. K., Lanza, I. R., Nair, S., Gores, G., et al. (2017) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00213.2016 · Cited by 75 · see citing works
Peiseler, M., & Tacke, F. (2021) · Cancers · doi:10.3390/cancers13040730 · Cited by 71 · see citing works
Hirsova, P., Bamidele, A. O., Wang, H., Povero, D., & Revelo, X. S. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.760860 · Cited by 70 · see citing works
Hepatic Macrophage as a Key Player in Fatty Liver Disease
Xu, L., Liu, W., Bai, F., Xu, Y., Liang, X., Ma, C., & Gao, L. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.708978 · Cited by 72 · see citing works
Immunomodulatory functions of FXR
Fiorucci, S., Zampella, A., Ricci, P., Distrutti, E., & Biagioli, M. (2022) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2022.111650 · Cited by 73 · see citing works
The immune landscape in nonalcoholic steatohepatitis
Narayanan, S., Surette, F. A., & Hahn, Y. S. (2016) · Immune Network · doi:10.4110/in.2016.16.3.147 · Cited by 64 · see citing works
Bojmar, L., Zambirinis, C. P., Hernandez, J. M., Chakraborty, J., Shaashua, L., Kim, J., Johnson, K. E., Hanna, S., Aşkan, G., Burman, J., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-03075-7 · Cited by 64 · see citing works
Self-citationImmunological Mechanisms in the Pathophysiology of Non-Alcoholic Steatohepatitis
Vonghia, L., Michielsen, P. P., & Francque, S. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms141019867 · Cited by 64 · see citing works
Campisano, S., la Colla, A. B., Echarte, S. M., & Chisari, A. N. (2019) · Nutrition Research Reviews · doi:10.1017/s0954422418000239 · Cited by 59 · see citing works
Moayedfard, Z., Sani, F., Alizadeh, A. A., Lankarani, K. B., Zarei, M., & Azarpira, N. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-022-02929-6 · Cited by 59 · see citing works
VanSaun, M. N., Mendonsa, A. M., & Gorden, D. L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073054 · Cited by 58 · see citing works
Treating inflammation to combat non-alcoholic fatty liver disease
Wiering, L., & Tacke, F. (2022) · Journal of Endocrinology · doi:10.1530/joe-22-0194 · Cited by 58 · see citing works
Wu, L., Gao, X., Guo, Q., Li, J., Yao, J., Yan, K., Xu, Y., Jiang, X., Ye, D., & Guo, J. (2020) · Hepatology International · doi:10.1007/s12072-020-10081-7 · Cited by 52 · see citing works
Fan, Y., Zhang, W., Wei, H.-M., Sun, R., Tian, Z., & Chen, Y.-Y. (2019) · Liver international (Print) · doi:10.1111/liv.14307 · Cited by 49 · see citing works
Maradana, M. R., Yekollu, S. K., Zeng, B., Ellis, J. J., Clouston, A. D., Miller, G. C., Talekar, M., Bhuyan, Z. A., Mahadevaiah, S., Powell, E. E., et al. (2017) · Metabolism · doi:10.1016/j.metabol.2017.09.002 · Cited by 51 · see citing works
Self-citationMa, C., Zhang, Q., & Greten, T. F. (2017) · FEBS Journal · doi:10.1111/febs.14209 · Cited by 48 · see citing works
Nakao, T., Ono, Y., Dai, H., Nakano, R., Pérez-Gutiérrez, A., Camirand, G., Huang, H., Geller, D. A., & Thomson, A. W. (2018) · Hepatology · doi:10.1002/hep.30334 · Cited by 47 · see citing works
Immunological distinctions between nonalcoholic steatohepatitis and hepatocellular carcinoma
Koo, S.-Y., Park, E.-J., & Lee, C.-W. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0480-3 · Cited by 47 · see citing works
Hepatic Dendritic Cells in the Development and Progression of Metabolic Steatohepatitis
Méndez‐Sánchez, N., Córdova‐Gallardo, J., Barranco-Fragoso, B., & Eslam, M. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.641240 · Cited by 47 · see citing works
Adapted Immune Responses of Myeloid-Derived Cells in Fatty Liver Disease
Hundertmark, J., Krenkel, O., & Tacke, F. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02418 · Cited by 45 · see citing works
Inflammation and Fibrogenesis in MAFLD: Role of the Hepatic Immune System
Torre, P., Motta, B. M., Sciorio, R., Masarone, M., & Persico, M. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.781567 · Cited by 47 · see citing works
Stress kinases in the development of liver steatosis and hepatocellular carcinoma
Cicuéndez, B., Ruiz-Garrido, I., Mora, A., & Sabio, G. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101190 · Cited by 45 · see citing works
The role of immune mechanisms in alcoholic and nonalcoholic steatohepatitis: a 2015 update
Sutti, S., Bruzzì, S., & Albano, E. (2016) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/17474124.2016.1111758 · Cited by 40 · see citing works
Chatzigeorgiou, A., & Chavakis, T. (2016) · Handbook of Experimental Pharmacology · doi:10.1007/164_2015_8 · Cited by 48 · see citing works
The Role of Dendritic Cells in Fibrosis Progression in Nonalcoholic Fatty Liver Disease
Almeda‐Valdés, P., Olivos, N. E. A., Barranco-Fragoso, B., Uribe, M., & Méndez‐Sánchez, N. (2015) · BioMed Research International · doi:10.1155/2015/768071 · Cited by 41 · see citing works
The immune response as a therapeutic target in non-alcoholic fatty liver disease
Ortiz‐López, N., Fuenzalida, C., Dufeu, M. S., Pinto-León, A., Escobar, A. F., Poníachik, J., Roblero, J. P., Valenzuela-Pérez, L., & Beltrán, C. J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.954869 · Cited by 35 · see citing works
Non-alcoholic fatty liver disease: Immunological mechanisms and current treatments
Petagine, L., Zariwala, M. G., & Patel, V. B. (2023) · World Journal of Gastroenterology · doi:10.3748/wjg.v29.i32.4831 · Cited by 37 · see citing works
CX3CR1 Mediates the Development of Monocyte-Derived Dendritic Cells during Hepatic Inflammation
Sutti, S., Bruzzì, S., Heymann, F., Liepelt, A., Krenkel, O., Toscani, A., Ramavath, N., Cotella, D., Albano, E., & Tacke, F. (2019) · Cells · doi:10.3390/cells8091099 · Cited by 34 · see citing works
Biagioli, M., & Fiorucci, S. (2021) · Liver Research · doi:10.1016/j.livres.2021.08.003 · Cited by 33 · see citing works
The microenvironment in the development of MASLD-MASH-HCC and associated therapeutic in MASH-HCC
Wu, Q., Yang, Y., Lin, S., Geller, D. A., & Yan, Y. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1569915 · Cited by 32 · see citing works
Immunoregulation by lipids during the development of non-alcoholic steatohepatitis.
Ramadori, P., Kroy, D. C., & Streetz, K. L. (2015) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2304-3881.2015.01.02 · Cited by 32 · see citing works
Mo, C., Xie, S., Liu, B., Zhong, W., Zeng, T., Huang, S., Lai, Y., Deng, G., Zhou, C., Yan, W., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-020-03277-0 · Cited by 32 · see citing works
Art of Making Artificial Liver: Depicting Human Liver Biology and Diseases in Mice
Sugahara, G., Ishida, Y., Sun, J. C., Tateno, C., & Saito, T. (2020) · Seminars in Liver Disease · doi:10.1055/s-0040-1701444 · Cited by 31 · see citing works
Galle-Treger, L., Helou, D. G., Quach, C., Howard, E. D., Hurrell, B. P., Muench, G. R. A., Shafiei-Jahani, P., Painter, J. D., Iorga, A., Dara, L., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29174-y · Cited by 31 · see citing works
Liver regeneration microenvironment of hepatocellular carcinoma for prevention and therapy
Li, H., & Zhang, L. (2016) · Oncotarget · doi:10.18632/oncotarget.12101 · Cited by 29 · see citing works
Crucial role of T cells in NAFLD-related disease: A review and prospect
Mao, T., Yang, R. X., Luo, Y., & He, K. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1051076 · Cited by 29 · see citing works
From Nafld to NASH to Fibrosis to HCC: Role of Dendritic Cell Populations in the Liver
Tacke, F., & Yoneyama, H. (2013) · Hepatology · doi:10.1002/hep.26405 · Cited by 29 · see citing works
Bile acids and their receptors in hepatic immunity
Fiorucci, S., Marchianò, S., Distrutti, E., & Biagioli, M. (2025) · Liver Research · doi:10.1016/j.livres.2025.01.005 · Cited by 28 · see citing works
Yoshida, O., Kimura, S., Dou, L., Matta, B. M., Yokota, S., Ross, M. A., Geller, D. A., & Thomson, A. W. (2014) · American Journal of Transplantation · doi:10.1111/ajt.12757 · Cited by 26 · see citing works
Wu, R., Nakatsu, G., Zhang, X., & Yu, J. Q. (2015) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2016.1125883 · Cited by 26 · see citing works
Hildreth, A. D., Padilla, E. T., Tafti, R. Y., Legala, A. R., & O’Sullivan, T. E. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112141 · Cited by 25 · see citing works
Immune cells and metabolic dysfunction
Eheim, A. L., Medříková, D., & Herzig, S. (2013) · Seminars in Immunopathology · doi:10.1007/s00281-013-0403-7 · Cited by 25 · see citing works
Vonghia, L. (2015) · World Journal of Hepatology · doi:10.4254/wjh.v7.i15.1905 · Cited by 25 · see citing works
Dendritic cells: understanding ontogeny, subsets, functions, and their clinical applications
Li, W., Yu, C., Zhang, X., Gu, Y., He, X., Xu, R., Xu, J. F., Yu, G., & Wu, Y. (2025) · Molecular Biomedicine · doi:10.1186/s43556-025-00300-8 · Cited by 28 · see citing works
Vonghia, L., Herck, M. A. V., Weyler, J., & Francque, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00563 · Cited by 24 · see citing works
Innate Immune System in the Pathogenesis of Non-Alcoholic Fatty Liver Disease
Ma, D. W., Ha, J., Yoon, K., Kang, I., Choi, T. G., & Kim, S. S. (2023) · Nutrients · doi:10.3390/nu15092068 · Cited by 24 · see citing works
Song, Y., Li, N., Jiang, S., Wang, K., Lv, G., Fan, Z., Du, X., Gao, W., Lei, L., Wang, Z., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-57574-3 · Cited by 24 · see citing works
Pathogenesis from Inflammation to Cancer in NASH-Derived HCC
Yu, S., Wang, J., Zheng, H., Wang, R., Johnson, N. L., Li, T., Li, P., Lin, J., Li, Y., Jin, Y., et al. (2022) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s377768 · Cited by 23 · see citing works
Fatty acid-driven modifications in T-cell profiles in non-alcoholic fatty liver disease patients
Seike, T., Mizukoshi, E., Yamada, K., Okada, H., Kitahara, M., Yamashita, T., Arai, K., Terashima, T., Iida, N., Fushimi, K., et al. (2020) · Journal of Gastroenterology · doi:10.1007/s00535-020-01679-7 · Cited by 22 · see citing works
Giurini, E. F., Ralph, O. G., Pappas, S. G., & Gupta, K. H. (2024) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-24-0311 · Cited by 21 · see citing works
Larner, D. P., Morgan, S., Gathercole, L., Doig, C. L., Guest, P., Weston, C. J., Hazeldine, J., Tomlinson, J., Stewart, P. M., & Lavery, G. G. (2016) · Endocrinology · doi:10.1210/en.2016-1357 · Cited by 20 · see citing works
- Authors
- Henning, J. R., Graffeo, C. S., Rehman, A., Fallon, N. C., Zambirinis, C. P., Ochi, A., Barilla, R., Jamal, M., Deutsch, M., Greco, S., Ego-Osuala, M., Bin-Saeed, U., Rao, R. S., Badar, S., Quesada, J. P., Acehan, D., & Miller, G.
- Affiliations
- New York University (US)
- Corresponding author
- Miller, George
- ORCID
- Venue
- Hepatology
- Published
- 2013-08
- Volume
- 58
- Issue
- 2
- Pages
- 589-602
- ISSN
- 0270-9139 (ISSN-L)
- PMC
- PMC3638069
- OpenAlex
- W2135810789
- Cited by
- 185
- References
- 43
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 15 · 2023: 15 · 2022: 24 · 2021: 15 · 2020: 13 · 2019: 15 · 2018: 8 · 2017: 11 · 2016: 14 · 2015: 14 · 2014: 8 · 2013: 8
- FWCI
- 10.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (CA155649, R21CA155649)
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK085278, DK085278)
- National Center for Research Resources (UL1RR029893)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- dendritic cells, nonalcoholic steatohepatitis, liver fibrosis, sterile inflammation, efferocytosis, CD8+ T cells, Toll-like receptors, Kupffer cells, neutrophils, inflammatory monocytes, liver cirrhosis
- MeSH terms
- Animals, Cell Communication, Cells, Cultured, Dendritic Cells, Disease Models, Animal, Fatty Liver, Kupffer Cells, Liver, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Necrosis, Neutrophils, Apoptosis, CD8-Positive T-Lymphocytes, Disease Progression, Toll-Like Receptors, Mice
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