| First Author | Simonian PL | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 1 | Pages | 657-65 |
| PubMed ID | 19109199 | Mgi Jnum | J:142879 |
| Mgi Id | MGI:3822376 | Doi | 10.4049/jimmunol.182.1.657 |
| Citation | Simonian PL, et al. (2009) Th17-polarized immune response in a murine model of hypersensitivity pneumonitis and lung fibrosis. J Immunol 182(1):657-65 |
| 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. |
