rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2008-12-25
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pubmed:abstractText |
Hypersensitivity pneumonitis is an environmental lung disease characterized by a diffuse mononuclear cell infiltrate in the lung that can progress to pulmonary fibrosis with chronic exposure to an inhaled Ag. Using a well-established murine model of hypersensitivity pneumonitis, we repeatedly exposed C57BL/6 mice to Saccharopolyspora rectivirgula to investigate whether T cells are required for lung fibrosis. In the absence of alphabeta T cells, TCRbeta(-/-) mice exposed to S. rectivirgula for 4 wk had markedly decreased mononuclear infiltrates and collagen deposition in the lung compared with wild-type C57BL/6 mice. In contrast to CD8(+) T cells, adoptive transfer of CD4(+) T cells reconstituted the S. rectivirgula-induced inflammatory and fibrotic response, suggesting that the CD4(+) T cell represents the critical alphabeta T cell subset. Cytokine analysis of lung homogenates at various time points after S. rectivirgula exposure failed to identify a predominant Th1 or Th2 phenotype. Conversely, IL-17 was found in the lung at increasing concentrations with continued exposure to S. rectivirgula. Intracellular cytokine staining revealed that 14% of CD4(+) T cells from the lung of mice treated with S. rectivirgula expressed IL-17A. In the absence of IL-17 receptor signaling, Il17ra(-/-) mice had significantly decreased lung inflammation and fibrosis compared with wild-type C57BL/6 mice. These data are the first to demonstrate an important role for Th17-polarized CD4(+) T lymphocytes in the immune response directed against S. rectivirgula in this murine model of hypersensitivity pneumonitis and pulmonary fibrosis.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1550-6606
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
182
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
657-65
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pubmed:dateRevised |
2011-5-6
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pubmed:meshHeading |
pubmed-meshheading:19109199-Animals,
pubmed-meshheading:19109199-Mice,
pubmed-meshheading:19109199-Female,
pubmed-meshheading:19109199-Pulmonary Fibrosis,
pubmed-meshheading:19109199-Disease Models, Animal,
pubmed-meshheading:19109199-Farmer's Lung,
pubmed-meshheading:19109199-Mice, Inbred C57BL,
pubmed-meshheading:19109199-Alveolitis, Extrinsic Allergic,
pubmed-meshheading:19109199-Adoptive Transfer,
pubmed-meshheading:19109199-T-Lymphocytes, Helper-Inducer,
pubmed-meshheading:19109199-Receptors, Antigen, T-Cell, gamma-delta,
pubmed-meshheading:19109199-Immunophenotyping,
pubmed-meshheading:19109199-Mice, Transgenic
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