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Immune tolerance: what is unique about the liver.
J Autoimmun. 2010 Feb; 34(1):1-6.JA

Abstract

The 'liver tolerance effect' mediates local and systemic tolerance to self and foreign antigens and has been attributed to specialized resident cells expressing anti-inflammatory mediators and inhibitory cell surface ligands for T cell activation. Non-parenchymal liver cells responsible for the tolerogenic properties of the liver are the resident dendritic cells (DCs), which comprise myeloid as well as plasmacytoid DCs, liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs) as well as hepatic stellate cells (HSCs), also known as Ito cells. These cells mediate immunosuppression by production of anti-inflammatory cytokines such as IL-10 and TGFbeta as well as by expression of the negative co-stimulator for T cell activation programmed cell death ligand-1 (PD-L1). An interesting observation in this context is that knockout of IL-10 or PD-L1 (or the receptor PD-1) does not necessarily result in inflammatory liver damage whereas transgenic inhibition of TGFbeta signaling induces liver disease in mice resembling chronic cholangitis. However, depending on the mouse model and on the type of injury, e.g. autoimmune disease, allograft rejection or viral infection, IL-10 or TGFbeta and/or PD-1 as well as cytotoxic T lymphocyte antigen-4 (CTLA-4) contribute to the immunosuppressive mechanisms of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), which seem to be converted in the liver from infiltrating conventional naïve CD4(+) T cells and/or effector CD4(+) T cells to control the disease. Finally, hepatocytes also contribute to the 'liver tolerance effect' by expression of MHC class II molecules, probably low levels of co-stimulatory molecules and high levels of the co-inhibitory molecule PD-L1.

Authors+Show Affiliations

Division of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. g.tiegs@uke.deNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

19717280

Citation

Tiegs, Gisa, and Ansgar W. Lohse. "Immune Tolerance: what Is Unique About the Liver." Journal of Autoimmunity, vol. 34, no. 1, 2010, pp. 1-6.
Tiegs G, Lohse AW. Immune tolerance: what is unique about the liver. J Autoimmun. 2010;34(1):1-6.
Tiegs, G., & Lohse, A. W. (2010). Immune tolerance: what is unique about the liver. Journal of Autoimmunity, 34(1), 1-6. https://doi.org/10.1016/j.jaut.2009.08.008
Tiegs G, Lohse AW. Immune Tolerance: what Is Unique About the Liver. J Autoimmun. 2010;34(1):1-6. PubMed PMID: 19717280.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immune tolerance: what is unique about the liver. AU - Tiegs,Gisa, AU - Lohse,Ansgar W, Y1 - 2009/08/29/ PY - 2009/08/12/received PY - 2009/08/13/accepted PY - 2009/9/1/entrez PY - 2009/9/1/pubmed PY - 2010/6/15/medline SP - 1 EP - 6 JF - Journal of autoimmunity JO - J Autoimmun VL - 34 IS - 1 N2 - The 'liver tolerance effect' mediates local and systemic tolerance to self and foreign antigens and has been attributed to specialized resident cells expressing anti-inflammatory mediators and inhibitory cell surface ligands for T cell activation. Non-parenchymal liver cells responsible for the tolerogenic properties of the liver are the resident dendritic cells (DCs), which comprise myeloid as well as plasmacytoid DCs, liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs) as well as hepatic stellate cells (HSCs), also known as Ito cells. These cells mediate immunosuppression by production of anti-inflammatory cytokines such as IL-10 and TGFbeta as well as by expression of the negative co-stimulator for T cell activation programmed cell death ligand-1 (PD-L1). An interesting observation in this context is that knockout of IL-10 or PD-L1 (or the receptor PD-1) does not necessarily result in inflammatory liver damage whereas transgenic inhibition of TGFbeta signaling induces liver disease in mice resembling chronic cholangitis. However, depending on the mouse model and on the type of injury, e.g. autoimmune disease, allograft rejection or viral infection, IL-10 or TGFbeta and/or PD-1 as well as cytotoxic T lymphocyte antigen-4 (CTLA-4) contribute to the immunosuppressive mechanisms of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), which seem to be converted in the liver from infiltrating conventional naïve CD4(+) T cells and/or effector CD4(+) T cells to control the disease. Finally, hepatocytes also contribute to the 'liver tolerance effect' by expression of MHC class II molecules, probably low levels of co-stimulatory molecules and high levels of the co-inhibitory molecule PD-L1. SN - 1095-9157 UR - https://www.unboundmedicine.com/medline/citation/19717280/Immune_tolerance:_what_is_unique_about_the_liver_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0896-8411(09)00105-X DB - PRIME DP - Unbound Medicine ER -