Liver Immunology

Overview

Journal Compr Physiol

Specialty Physiology

Date 2013 May 31

PMID 23720323

Citations 97

Authors

Dimitrios P Bogdanos

Bin Gao

M Eric Gershwin

Affiliations

Soon will be listed here.

Abstract

The liver is the largest organ in the body and is generally regarded by nonimmunologists as having little or no lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and it is instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena, which if not controlled by regulatory lymphoid populations, may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events that lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discuss selected, but not all, immune-mediated liver disease and attempt to place these data in the context of human autoimmunity.

Citing Articles

Cellular and immune landscape of chronic liver diseases: insights from immunophenotyping.

Soleimani S, Albayrak O, Somay K, Yang H, Yigit B, Ulukan B Front Mol Biosci. 2025; 11:1521811.

PMID: 39944754 PMC: 11813787. DOI: 10.3389/fmolb.2024.1521811.

Curcumin and Its Derivatives in Hepatology: Therapeutic Potential and Advances in Nanoparticle Formulations.

Karatayli E, Sadiq S, Schattenberg J, Grabbe S, Biersack B, Kaps L Cancers (Basel). 2025; 17(3).

PMID: 39941855 PMC: 11816286. DOI: 10.3390/cancers17030484.

Regulatory role of S1P and its receptors in sepsis-induced liver injury.

Wang B, Wu X, Cheng J, Ye J, Zhu H, Liu X Front Immunol. 2025; 16:1489015.

PMID: 39935473 PMC: 11811114. DOI: 10.3389/fimmu.2025.1489015.

Harnessing nanoparticles for reshaping tumor immune microenvironment of hepatocellular carcinoma.

Li J, Zhang G, Li G, Zhang J, Yang Z, Yang L Discov Oncol. 2025; 16(1):121.

PMID: 39909958 PMC: 11799483. DOI: 10.1007/s12672-025-01897-6.

FrozONE: quick cell nucleus enrichment for comprehensive proteomics analysis of frozen tissues.

Huschet L, Kliem F, Wienand P, Wunderlich C, Ribeiro A, Bustos-Martinez I Life Sci Alliance. 2024; 8(3).

PMID: 39667914 PMC: 11638322. DOI: 10.26508/lsa.202403130.

References

Shoukry N, Grakoui A, Houghton M, Chien D, Ghrayeb J, Reimann K . Memory CD8+ T cells are required for protection from persistent hepatitis C virus infection. J Exp Med. 2003; 197(12):1645-55. PMC: 2193956. DOI: 10.1084/jem.20030239. View

Van de Water J, Ansari A, Prindiville T, Coppel R, Ricalton N, Kotzin B . Heterogeneity of autoreactive T cell clones specific for the E2 component of the pyruvate dehydrogenase complex in primary biliary cirrhosis. J Exp Med. 1995; 181(2):723-33. PMC: 2191887. DOI: 10.1084/jem.181.2.723. View

Berg P, Doniach D, Roitt I . Mitochondrial antibodies in primary biliary cirrhosis. I. Localization of the antigen to mitochondrial membranes. J Exp Med. 1967; 126(2):277-90. PMC: 2138313. DOI: 10.1084/jem.126.2.277. View

Longhi M, Meda F, Wang P, Samyn M, Mieli-Vergani G, Vergani D . Expansion and de novo generation of potentially therapeutic regulatory T cells in patients with autoimmune hepatitis. Hepatology. 2008; 47(2):581-91. DOI: 10.1002/hep.22071. View

Lian Z, Okada T, He X, Kita H, Liu Y, Ansari A . Heterogeneity of dendritic cells in the mouse liver: identification and characterization of four distinct populations. J Immunol. 2003; 170(5):2323-30. DOI: 10.4049/jimmunol.170.5.2323. View

Gabbiani G, RYAN G, LAMELIN J, Vassalli P, Majno G, BOUVIER C . Human smooth muscle autoantibody. Its identification as antiactin antibody and a study of its binding to "nonmuscular" cells. Am J Pathol. 1973; 72(3):473-88. PMC: 1904020. View

Calne R, Sells R, Pena J, Davis D, Millard P, HERBERTSON B . Induction of immunological tolerance by porcine liver allografts. Nature. 1969; 223(5205):472-6. DOI: 10.1038/223472a0. View

Van de Water J, Gershwin M, Leung P, Ansari A, Coppel R . The autoepitope of the 74-kD mitochondrial autoantigen of primary biliary cirrhosis corresponds to the functional site of dihydrolipoamide acetyltransferase. J Exp Med. 1988; 167(6):1791-9. PMC: 2189671. DOI: 10.1084/jem.167.6.1791. View

Urbani S, Amadei B, Tola D, Pedrazzi G, Sacchelli L, Cavallo M . Restoration of HCV-specific T cell functions by PD-1/PD-L1 blockade in HCV infection: effect of viremia levels and antiviral treatment. J Hepatol. 2008; 48(4):548-58. DOI: 10.1016/j.jhep.2007.12.014. View

10.

Lopes A, Kellam P, Das A, Dunn C, Kwan A, Turner J . Bim-mediated deletion of antigen-specific CD8 T cells in patients unable to control HBV infection. J Clin Invest. 2008; 118(5):1835-45. PMC: 2289792. DOI: 10.1172/JCI33402. View

11.

Pradel G, Frevert U . Malaria sporozoites actively enter and pass through rat Kupffer cells prior to hepatocyte invasion. Hepatology. 2001; 33(5):1154-65. DOI: 10.1053/jhep.2001.24237. View

12.

Lohse A, Knolle P, Bilo K, Uhrig A, Waldmann C, Ibe M . Antigen-presenting function and B7 expression of murine sinusoidal endothelial cells and Kupffer cells. Gastroenterology. 1996; 110(4):1175-81. DOI: 10.1053/gast.1996.v110.pm8613007. View

13.

Shimoda S, Van de Water J, Ansari A, Nakamura M, Ishibashi H, Coppel R . Identification and precursor frequency analysis of a common T cell epitope motif in mitochondrial autoantigens in primary biliary cirrhosis. J Clin Invest. 1998; 102(10):1831-40. PMC: 509133. DOI: 10.1172/JCI4213. View

14.

Probst H, Lagnel J, Kollias G, van den Broek M . Inducible transgenic mice reveal resting dendritic cells as potent inducers of CD8+ T cell tolerance. Immunity. 2003; 18(5):713-20. DOI: 10.1016/s1074-7613(03)00120-1. View

15.

Fattovich G . Natural history and prognosis of hepatitis B. Semin Liver Dis. 2003; 23(1):47-58. DOI: 10.1055/s-2003-37590. View

16.

Verkoczy L, Chen Y, Bouton-Verville H, Zhang J, Diaz M, Hutchinson J . Rescue of HIV-1 broad neutralizing antibody-expressing B cells in 2F5 VH x VL knockin mice reveals multiple tolerance controls. J Immunol. 2011; 187(7):3785-97. PMC: 3192533. DOI: 10.4049/jimmunol.1101633. View

17.

Knolle P, Schmitt E, Jin S, Germann T, Duchmann R, Hegenbarth S . Induction of cytokine production in naive CD4(+) T cells by antigen-presenting murine liver sinusoidal endothelial cells but failure to induce differentiation toward Th1 cells. Gastroenterology. 1999; 116(6):1428-40. DOI: 10.1016/s0016-5085(99)70508-1. View

18.

Li W, Kuhr C, Zheng X, Carper K, Thomson A, Reyes J . New insights into mechanisms of spontaneous liver transplant tolerance: the role of Foxp3-expressing CD25+CD4+ regulatory T cells. Am J Transplant. 2008; 8(8):1639-51. DOI: 10.1111/j.1600-6143.2008.02300.x. View

19.

Barber D, Wherry E, Masopust D, Zhu B, Allison J, Sharpe A . Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 2005; 439(7077):682-7. DOI: 10.1038/nature04444. View

20.

Bogdanos D, Dalekos G . Enzymes as target antigens of liver-specific autoimmunity: the case of cytochromes P450s. Curr Med Chem. 2008; 15(22):2285-92. DOI: 10.2174/092986708785747508. View