RGD Reference Report - Blockade of NKG2D on NKT cells prevents hepatitis and the acute immune response to hepatitis B virus. - Rat Genome Database

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Blockade of NKG2D on NKT cells prevents hepatitis and the acute immune response to hepatitis B virus.

Authors: Vilarinho, Sílvia  Ogasawara, Kouetsu  Nishimura, Stephen  Lanier, Lewis L  Baron, Jody L 
Citation: Vilarinho S, etal., Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18187-92. doi: 10.1073/pnas.0708968104. Epub 2007 Nov 8.
RGD ID: 38676490
Pubmed: PMID:17991774   (View Abstract at PubMed)
PMCID: PMC2084318   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0708968104   (Journal Full-text)

Hepatitis B virus (HBV) is a hepadnavirus that is a major cause of acute and chronic hepatitis in humans. Hepatitis B viral infection itself is noncytopathic, and it is the immune response to the viral antigens that is thought to be responsible for hepatic pathology. Previously, we developed a transgenic mouse model of primary HBV infection and demonstrated that the acute liver injury is mediated by nonclassical natural killer (NK)T cells, which are CD1d-restricted, but nonreactive to alpha-GalCer. We now demonstrate a role for NKG2D and its ligands in this nonclassical NKT cell-mediated immune response to hepatitis B virus and in the subsequent acute hepatitis that ensues. Surface expression of NKG2D and one of its ligands (retinoic acid early inducible-1 or RAE-1) are modulated in an HBV-dependent manner. Furthermore, blockade of an NKG2D-ligand interaction completely prevents the HBV- and CD1d-dependent, nonclassical NKT cell-mediated acute hepatitis and liver injury. This study has major implications for understanding activation of NKT cells and identifies a potential therapeutic target in treating hepatitis B viral infection.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Klrk1Rathepatitis B treatmentISOKlrk1 (Mus musculus) RGD 
Klrk1Mousehepatitis B treatmentIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Klrk1  (killer cell lectin like receptor K1)

Genes (Mus musculus)
Klrk1  (killer cell lectin-like receptor subfamily K, member 1)


Additional Information