Natural killer T cells within the liver: conductors of the hepatic immune orchestra
- PMID: 20460885
- DOI: 10.1159/000282059
Natural killer T cells within the liver: conductors of the hepatic immune orchestra
Abstract
Natural killer T (NKT) cells are distinct innate immune T cells which play a key role in the pathogenesis of various immune-mediated liver diseases. NKT cells are traditionally defined as cells that co-express the T cell receptor (TCR) and certain natural killer cell surface markers (e.g. NK1.1 in some mouse strains). Based on CD1d restriction, they are broadly classified as invariant (iNKT) and noninvariant NKT cells. Both NKT cell types are abundant within the liver and, mainly through the study of animal models of immune-mediated liver injury, the role of NKT cells in the context of liver inflammation is becoming better understood. iNKT cells are the NKT cell subtype which has been most well characterized, and therefore this paper will focus mainly on iNKT cells. NKT cells recognize both host and microbial glycolipid antigens, presented by antigen-presenting cells in the context of the MHC class I- like molecule CD1d, via their T cell receptor. Upon activation, NKT cells rapidly release large quantities of T helper type 1 (Th1; e.g. IFN-gamma, TNF-alpha), Th2 (e.g. IL-4, IL-10), and Th17 (e.g. IL-17, IL-22) type cytokines, with diverse immunoregulatory and immunomodulatory effects. Moreover, through the release of these cytokines, NKT cells can drive subsequent downstream immune responses in tissues such as the liver, including the upregulation of adhesion molecule expression and increased chemokine production. By regulating immune cell adhesion pathways and chemokine secretion, NKT cells can direct both pro-inflammatory (e.g. Th1 cell) and anti-inflammatory (e.g. regulatory T cell) cell infiltration into the liver. Through this mechanism, NKT cells orchestrate a balance between pro- and anti-inflammatory responses within the liver during immune-mediated liver damage. This paper highlights the diverse roles played by iNKT cells as master regulators of immune-mediated liver injury.
Copyright 2010 S. Karger AG, Basel.
Similar articles
-
Invariant and noninvariant natural killer T cells exert opposite regulatory functions on the immune response during murine schistosomiasis.Infect Immun. 2007 May;75(5):2171-80. doi: 10.1128/IAI.01178-06. Epub 2007 Mar 12. Infect Immun. 2007. PMID: 17353286 Free PMC article.
-
Invariant natural killer T cells: innate-like T cells with potent immunomodulatory activities.Tissue Antigens. 2009 Jun;73(6):535-45. doi: 10.1111/j.1399-0039.2009.01256.x. Epub 2009 Apr 8. Tissue Antigens. 2009. PMID: 19392798 Review.
-
NKT cell responses to glycolipid activation.Methods Mol Biol. 2010;626:149-67. doi: 10.1007/978-1-60761-585-9_11. Methods Mol Biol. 2010. PMID: 20099127
-
Cytokine-dependent modification of IL-12p70 and IL-23 balance in dendritic cells by ligand activation of Valpha24 invariant NKT cells.J Immunol. 2009 Jul 1;183(1):201-8. doi: 10.4049/jimmunol.0900873. J Immunol. 2009. PMID: 19542431
-
Hepatic NKT cells: friend or foe?Clin Sci (Lond). 2008 Apr;114(7):457-66. doi: 10.1042/CS20070328. Clin Sci (Lond). 2008. PMID: 18302533 Review.
Cited by
-
Targeting curcusomes to inflammatory dendritic cells inhibits NF-κB and improves insulin resistance in obese mice.Diabetes. 2011 Nov;60(11):2928-38. doi: 10.2337/db11-0275. Epub 2011 Sep 1. Diabetes. 2011. PMID: 21885868 Free PMC article.
-
Living in the liver: hepatic infections.Nat Rev Immunol. 2012 Feb 24;12(3):201-13. doi: 10.1038/nri3169. Nat Rev Immunol. 2012. PMID: 22362353 Review.
-
TNFα Augments Cytokine-Induced NK Cell IFNγ Production through TNFR2.J Innate Immun. 2016;8(6):617-629. doi: 10.1159/000448077. Epub 2016 Aug 25. J Innate Immun. 2016. PMID: 27560480 Free PMC article.
-
Invariant natural killer T cells contribute to chronic-plus-binge ethanol-mediated liver injury by promoting hepatic neutrophil infiltration.Cell Mol Immunol. 2016 Mar;13(2):206-16. doi: 10.1038/cmi.2015.06. Epub 2015 Feb 9. Cell Mol Immunol. 2016. PMID: 25661730 Free PMC article.
-
Innate immune responses in hepatitis C virus-exposed healthcare workers who do not develop acute infection.Hepatology. 2013 Nov;58(5):1621-31. doi: 10.1002/hep.26353. Epub 2013 Sep 30. Hepatology. 2013. PMID: 23463364 Free PMC article.
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Research Materials