Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2002-4-8
pubmed:abstractText
Dendritic cell (DC)-dependent activation of liver NKT cells triggered by a single i.v. injection of a low dose (10-100 ng/mouse) of alpha-galactosyl ceramide (alphaGalCer) into mice induces liver injury. This response is particularly evident in HBs-tg B6 mice that express a transgene-encoded hepatitis B surface Ag in the liver. Liver injury following alphaGalCer injection is suppressed in mice depleted of NK cells, indicating that NK cells play a role in NK T cell-initiated liver injury. In vitro, liver NKT cells provide a CD80/86-dependent signal to alphaGalCer-pulsed liver DC to release IL-12 p70 that stimulates the IFN-gamma response of NKT and NK cells. Adoptive transfer of NKT cell-activated liver DC into the liver of nontreated, normal (immunocompetent), or immunodeficient (RAG(-/-) or HBs-tg/RAG(-/-)) hosts via the portal vein elicited IFN-gamma responses of liver NK cells in situ. IFN-beta down-regulates the pathogenic IL-12/IFN-gamma cytokine cascade triggered by NKT cell/DC/NK cell interactions in the liver. Pretreating liver DC in vitro with IFN-beta suppressed their IL-12 (but not IL-10) release in response to CD40 ligation or specific (alphaGalCer-dependent) interaction with liver NKT cells and down-regulated the IFN-gamma response of the specifically activated liver NKT cells. In vivo, IFN-beta attenuated the NKT cell-triggered induction of liver immunopathology. This study identifies interacting subsets of the hepatic innate immune system (and cytokines that up- and down-regulate these interactions) activated early in immune-mediated liver pathology.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
168
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3763-70
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11937527-Adoptive Transfer, pubmed-meshheading:11937527-Animals, pubmed-meshheading:11937527-Antigens, CD, pubmed-meshheading:11937527-Antigens, CD80, pubmed-meshheading:11937527-Antigens, CD86, pubmed-meshheading:11937527-Cells, Cultured, pubmed-meshheading:11937527-Coculture Techniques, pubmed-meshheading:11937527-Cytotoxicity, Immunologic, pubmed-meshheading:11937527-Dendritic Cells, pubmed-meshheading:11937527-Galactosylceramides, pubmed-meshheading:11937527-Immunosuppressive Agents, pubmed-meshheading:11937527-Injections, Intravenous, pubmed-meshheading:11937527-Interferon-beta, pubmed-meshheading:11937527-Interleukin-12, pubmed-meshheading:11937527-Killer Cells, Natural, pubmed-meshheading:11937527-Liver, pubmed-meshheading:11937527-Lymphocyte Activation, pubmed-meshheading:11937527-Membrane Glycoproteins, pubmed-meshheading:11937527-Mice, pubmed-meshheading:11937527-Mice, Inbred C57BL, pubmed-meshheading:11937527-Mice, Knockout, pubmed-meshheading:11937527-Mice, Transgenic, pubmed-meshheading:11937527-T-Lymphocyte Subsets
pubmed:year
2002
pubmed:articleTitle
Activating immunity in the liver. II. IFN-beta attenuates NK cell-dependent liver injury triggered by liver NKT cell activation.
pubmed:affiliation
Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't