Linked Life Data

18209085

Source:http://linkedlifedata.com/resource/pubmed/id/18209085

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-1-22
pubmed:abstractText
TNF is a major therapeutic target in a range of chronic inflammatory disorders, including asthma. TNFR-associated factor (TRAF)1 is an intracellular adaptor molecule important for signaling by TNFR. In this study, we investigated the role of TRAF1 in an adoptive transfer model of allergic lung inflammation. Mice deficient in TRAF1 (TRAF1(-/-)) and wild-type (WT) control animals were adoptively transferred with WT OVA-immune CD4(+) T cells, exposed to an aerosol of LPS-free OVA, and analyzed for the development of allergic lung inflammation. In contrast to WT mice, TRAF1(-/-) recipients failed to display goblet cell hyperplasia, eosinophilic inflammation, and airway hyperresponsiveness in this model of asthma. Neither T cell recruitment nor expression of the proinflammatory cytokines IL-4, IL-5, IL-13, or TNF occurred in the lungs of TRAF1(-/-) mice. Although purified myeloid TRAF1(-/-) dendritic cells (DCs) exhibited normal Ag-presenting function and transmigratory capacity in vitro and were able to induce OVA-specific immune responses in the lung draining lymph nodes (LNs) following adoptive transfer in vivo, CD11c(+)CD11b(+) DCs from airways of TRAF1(-/-) recipients were not activated, and purified draining LN cells did not proliferate in vitro. Moreover, transfer of WT or TRAF1(-/-) DCs failed to restore T cell recruitment and DC activation in the airways of TRAF1(-/-) mice, suggesting that the expression of TRAF1 in resident lung cells is required for the development of asthma. Finally, we demonstrate that T cell-transfused TRAF1(-/-) recipient mice demonstrated impaired up-regulation of ICAM-1 expression on lung cells in response to OVA exposure.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
180
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1878-85
pubmed:meshHeading
pubmed-meshheading:18209085-Adoptive Transfer, pubmed-meshheading:18209085-Allergens, pubmed-meshheading:18209085-Animals, pubmed-meshheading:18209085-Antigen Presentation, pubmed-meshheading:18209085-Antigens, CD11b, pubmed-meshheading:18209085-Antigens, CD11c, pubmed-meshheading:18209085-Asthma, pubmed-meshheading:18209085-Dendritic Cells, pubmed-meshheading:18209085-Disease Models, Animal, pubmed-meshheading:18209085-Inhalation, pubmed-meshheading:18209085-Intercellular Adhesion Molecule-1, pubmed-meshheading:18209085-Lipopolysaccharides, pubmed-meshheading:18209085-Lung, pubmed-meshheading:18209085-Lymph Nodes, pubmed-meshheading:18209085-Mice, pubmed-meshheading:18209085-Mice, Mutant Strains, pubmed-meshheading:18209085-Ovalbumin, pubmed-meshheading:18209085-Pneumonia, pubmed-meshheading:18209085-Respiratory Hypersensitivity, pubmed-meshheading:18209085-T-Lymphocytes, pubmed-meshheading:18209085-TNF Receptor-Associated Factor 1
pubmed:year
2008
pubmed:articleTitle
TNF receptor-associated factor 1 expressed in resident lung cells is required for the development of allergic lung inflammation.
pubmed:affiliation
CBR Institute for Biomedical Research, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural