Marcellin P, Kutala BK. Liver diseases: a major, neglected global public health problem requiring urgent actions and large-scale screening. Liver Int. 2018;38:2–6.
Younossi ZM, Wong G, Anstee QM, Henry L. The global burden of liver disease. Clin Gastroenterol Hepatol. 2023;21:1978–91.
Mackowiak B, Fu Y, Maccioni L, Gao B. Alcohol-associated liver disease. J Clin Investig. 2024;134. https://doi.org/10.1172/JCI176345.
Åberg F, Byrne CD, Pirola CJ, Männistö V, Sookoian S. Alcohol consumption and metabolic syndrome: clinical and epidemiological impact on liver disease. J Hepatol. 2023;78:191–206.
Lan Y, Wang H, Weng H, Xu X, Yu X, Tu H, et al. The burden of liver cirrhosis and underlying etiologies: results from the Global Burden of Disease Study 2019. Hepatol Commun. 2023;7:e0026.
PubMed PubMed Central Google Scholar
Paik JM, Golabi P, Younossi Y, Mishra A, Younossi ZM. Changes in the global burden of chronic liver diseases from 2012 to 2017: the growing impact of NAFLD. Hepatology. 2020;72. https://doi.org/10.1002/hep.31173/suppinfo.
Tacke F, Horn P, Wai-Sun Wong V, Ratziu V, Bugianesi E, Francque S, et al. EASL–EASD–EASO clinical practice guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol. 2024;81:492–542.
Liu K, Wang FS, Xu R. Neutrophils in liver diseases: pathogenesis and therapeutic targets. Cell Mol Immunol. 2021;18:38–44. https://doi.org/10.1038/s41423-020-00560-0.
Bernsmeier C, van der Merwe S, Périanin A. Innate immune cells in cirrhosis. J Hepatol. 2020;73. https://doi.org/10.1016/j.jhep.2020.03.027.
Hahn JW, Yang HR, Moon JS, Chang JY, Lee K, Kim GA et al. Global incidence and prevalence of autoimmune hepatitis, 1970–2022: a systematic review and meta-analysis. EClinicalMed. 2023;65. https://doi.org/10.1016/j.eclinm.2023.102280.
European Association for the Study of the Liver. EASL clinical practice guidelines: the diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017;67:145–72.
Chazouilleres O, Beuers U, Bergquist A, Karlsen TH, Levy C, Samyn M, et al. EASL clinical practice guidelines on sclerosing cholangitis. J Hepatol. 2022;77:761–806.
Karlsen TH, Folseraas T, Thorburn D, Vesterhus M. Primary sclerosing cholangitis—a comprehensive review. J Hepatol. 2017;67:1298–323.
Schwabe RF, Brenner DA. Hepatic stellate cells: balancing homeostasis, hepatoprotection and fibrogenesis in health and disease. Nat Rev Gastroenterol Hepatol. 2025. https://doi.org/10.1038/s41575-025-01068-6.
Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, et al. Hepatocellular carcinoma. Nat Rev Dis Prim. 2021;7:6.
Brindley PJ, Bachini M, Ilyas SI, Khan SA, Loukas A, Sirica AE et al. Cholangiocarcinoma. Nat Rev Dis Primers. 2021;7. https://doi.org/10.1038/s41572-021-00300-2.
Ben-Moshe S, Itzkovitz S. Spatial heterogeneity in the mammalian liver. Nat Rev Gastroenterol Hepatol. 2019;16:395–410.
Gao B, Jeong W-I, Tian Z. Liver: an organ with predominant innate immunity. Hepatology. 2008;47:729–36.
Nemeth E, Baird AW, O’Farrelly C. Microanatomy of the liver immune system. Semin Immunopathol. 2009;31:333–43.
Cheng X, Kim SY, Okamoto H, Xin Y, Yancopoulos GD, Murphy AJ, et al. Glucagon contributes to liver zonation. Proc Natl Acad Sci USA. 2018;115:E4111–19.
CAS PubMed PubMed Central Google Scholar
Paris J, Henderson NC. Liver zonation, revisited. Hepatology. 2022;76:1219–30.
Kawashima K, Andreata F, Beccaria CG, Iannacone M. Priming and maintenance of adaptive immunity in the liver. Annu Rev Immunol. 2024;42:375–99.
Halpern KB, Shenhav R, Matcovitch-Natan O, Tóth B, Lemze D, Golan M, et al. Single-cell spatial reconstruction reveals global division of labor in the mammalian liver. Nature. 2017;542:352–6.
CAS PubMed PubMed Central Google Scholar
MacParland SA, Liu JC, Ma XZ, Innes BT, Bartczak AM, Gage BK et al. Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations. Nat Commun. 2018;9. https://doi.org/10.1038/s41467-018-06318-7.
Aizarani N, Saviano A, Sagar, Mailly L, Durand S, Herman JS, et al. A human liver cell atlas reveals heterogeneity and epithelial progenitors. Nature. 2019;572:199–204.
CAS PubMed PubMed Central Google Scholar
Halpern KB, Shenhav R, Massalha H, Toth B, Egozi A, Massasa EE, et al. Paired-cell sequencing enables spatial gene expression mapping of liver endothelial cells. Nat Biotechnol. 2018;36:962–70.
CAS PubMed PubMed Central Google Scholar
Dobie R, Wilson-Kanamori JR, Henderson BEP, Smith JR, Matchett KP, Portman JR, et al. Single-cell transcriptomics uncovers zonation of function in the mesenchyme during liver fibrosis. Cell Rep. 2019;29:1832–47.e8.
CAS PubMed PubMed Central Google Scholar
Gola A, Dorrington MG, Speranza E, Sala C, Shih RM, Radtke AJ, et al. Commensal-driven immune zonation of the liver promotes host defense. Nature. 2021;589:131–6.
Guilliams M, Bonnardel J, Haest B, Vanderborght B, Wagner C, Remmerie A, et al. Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches. Cell. 2022;185:379–96.e38.
CAS PubMed PubMed Central Google Scholar
Miyamoto Y, Kikuta J, Matsui T, Hasegawa T, Fujii K, Okuzaki D, et al. Periportal macrophages protect against commensal-driven liver inflammation. Nature. 2024;629:901–9.
Strnad P, Tacke F, Koch A, Trautwein C. Liver-guardian, modifier and target of sepsis. Nat Rev Gastroenterol Hepatol. 2017;14:55–66.
Kubes P, Jenne C. Immune responses in the liver. Annu Rev Immunol. 2018;36:247–77.
Stamataki Z, Swadling L. The liver as an immunological barrier redefined by single-cell analysis. Immunology. 2020;160:157–70.
CAS PubMed PubMed Central Google Scholar
Jenne CN, Kubes P. Immune surveillance by the liver. Nat Immunol. 2013;14:996–1006.
Campana L, Esser H, Huch M, Forbes S. Liver regeneration and inflammation: from fundamental science to clinical applications. Nat Rev Mol Cell Biol. 2021;22:608–24.
Robinson MW, Harmon C, O’Farrelly C. Liver immunology and its role in inflammation and homeostasis. Cell Mol Immunol. 2016;13:267–76.
CAS PubMed PubMed Central Google Scholar
Sun D, Sun P, Li H, Zhang M, Liu G, Strickland AB et al. Fungal dissemination is limited by liver macrophage filtration of the blood. Nat Commun. 2019;10. https://doi.org/10.1038/s41467-019-12381-5.
Zhao D, Yang F, Wang Y, Li S, Li Y, Hou F et al. ALK1 signaling is required for the homeostasis of Kupffer cells and prevention of bacterial infection. J Clin Investig. 2022;132. https://doi.org/10.1172/JCI150489.
Blériot C, Dupuis T, Jouvion G, Eberl G, Disson O, Lecuit M. Liver-resident macrophage necroptosis orchestrates type 1 microbicidal inflammation and type-2-mediated tissue repair during bacterial infection. Immunity. 2015;42:145–58.
Peiseler M, Araujo David B, Zindel J, Surewaard BGJ, Lee W-Y, Heymann F, et al. Kupffer cell-like syncytia replenish resident macrophage function in the fibrotic liver. Science. 2023;381:eabq5202.
Triantafyllou E, Gudd CL, Mawhin M-A, Husbyn HC, Trovato FM, Siggins MK et al. PD-1 blockade improves kupffer cell bacterial clearance in acute liver injury. J Clin Investig. 2021;131. https://doi.org/10.1172/JCI140196.
Balmer ML, Slack E, de Gottardi A, Lawson MAE, Hapfelmeier S, Miele L, et al. The liver may act as a firewall mediating mutualism between the host and its gut commensal microbiota. Sci Transl Med. 2014;6:237ra66.
David BA, Rezende RM, Antunes MM, Santos MM, Freitas Lopes MA, Diniz AB, et al. Combination of mass cytometry and imaging analysis reveals origin, location, and functional repopulation of liver myeloid cells in mice. Gastroenterology. 2016;151:1176–91.
Zeng Z, Surewaard BGJ, Wong CHY, Geoghegan JA, Jenne CN, Kubes P. CRIg functions as a macrophage pattern recognition receptor to directly bind and capture blood-borne gram-positive bacteria. Cell Host Microbe. 2016;20:99–106.
Nakagaki BN, Mafra K, de Carvalho É, Lopes ME, Carvalho-Gontijo R, de Castro-Oliveira HM, et al. Immune and metabolic shifts during neonatal development reprogram liver identity and function. J Hepatol. 2018;69:1294–307.
Zeng Z, Surewaard BGJ, Wong CHY, Guettler C, Petri B, Burkhard R, et al. Sex-hormone-driven innate antibodies protect females and infants against EPEC infection. Nat Immunol. 2018;19:1100–11.
Wang J, An H, Ding M, Liu Y, Wang S, Jin Q, et al. Liver macrophages and sinusoidal endothelial cells execute vaccine-elicited capture of invasive bacteria. Sci Transl Med. 2023;15:eade0054.
Araujo David B, Atif J, Vargas e Silva Castanheira F, Yasmin T, Guillot A, Ait Ahmed Y, Peiseler M, et al. Kupffer cell reverse migration into the liver sinusoids mitigates neonatal sepsis and meningitis. Sci Immunol. 2024;9:eadq9704.
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