Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-3-7
pubmed:abstractText
Dendritic cell (DC) maturation at the site of inflammation and migration into draining lymph nodes is fundamental to initiate Ag-specific immune responses. Although several proinflammatory cytokines, including IL-1, are known to promote DC maturation in vitro, their contributions to DC activation and migration within peripheral inflamed tissue compartments are not yet fully understood. We show here that endogenous IL-1 receptor antagonist (IL-1ra) controls the activation state of liver-recruited DCs and their migration in a Propionibacterium acnes-induced murine granulomatous liver disease model. After P. acnes treatment, formation of portal tract-associated lymphoid tissue was conversely impaired in IL-1ra-deficient mice. IL-1ra-deficient mice developed hepatic granulomas within 3 days after P. acnes administration and showed a more pronounced granuloma formation than wild-type mice. Although sinusoidal granulomas contained numerous CD11c+ DCs at day 7, expressions of CCR7, IL-12p40 by these DCs were dramatically decreased in IL-1ra-deficient mice, suggesting aberrant DC maturation and sinusoid portal migration in the absence of endogenous IL-1ra. This was accompanied with enhanced intrahepatic Th2 cytokine production and severe hepatocellular damage. Thus, hepatocyte-derived IL-1ra may control optimal activation and migration of inflammatory DCs within the liver and thereby determine the local immune responses in granulomatous liver disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
174
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3273-80
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15749858-Animals, pubmed-meshheading:15749858-Base Sequence, pubmed-meshheading:15749858-Cell Differentiation, pubmed-meshheading:15749858-Cell Movement, pubmed-meshheading:15749858-Cytokines, pubmed-meshheading:15749858-DNA, pubmed-meshheading:15749858-Dendritic Cells, pubmed-meshheading:15749858-Granuloma, pubmed-meshheading:15749858-Interleukin 1 Receptor Antagonist Protein, pubmed-meshheading:15749858-Liver Diseases, pubmed-meshheading:15749858-Mice, pubmed-meshheading:15749858-Mice, Inbred C57BL, pubmed-meshheading:15749858-Mice, Knockout, pubmed-meshheading:15749858-Models, Immunological, pubmed-meshheading:15749858-Propionibacterium acnes, pubmed-meshheading:15749858-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15749858-Sialoglycoproteins, pubmed-meshheading:15749858-Th2 Cells
pubmed:year
2005
pubmed:articleTitle
Exacerbation of granuloma formation in IL-1 receptor antagonist-deficient mice with impaired dendritic cell maturation associated with Th2 cytokine production.
pubmed:affiliation
Department of Molecular Preventive Medicine, School of Medicine, University of Tokyo, Japan.
pubmed:publicationType
Journal Article