| First Author | Fogli LK | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 6 | Pages | 3100-11 |
| PubMed ID | 23966625 | Mgi Jnum | J:205858 |
| Mgi Id | MGI:5546543 | Doi | 10.4049/jimmunol.1301360 |
| Citation | Fogli LK, et al. (2013) T cell-derived IL-17 mediates epithelial changes in the airway and drives pulmonary neutrophilia. J Immunol 191(6):3100-11 |
| abstractText | Th17 cells are a proinflammatory subset of effector T cells that have been implicated in the pathogenesis of asthma. Their production of the cytokine IL-17 is known to induce local recruitment of neutrophils, but the direct impact of IL-17 on the lung epithelium is poorly understood. In this study, we describe a novel mouse model of spontaneous IL-17-driven lung inflammation that exhibits many similarities to asthma in humans. We have found that STAT3 hyperactivity in T lymphocytes causes an expansion of Th17 cells, which home preferentially to the lungs. IL-17 secretion then leads to neutrophil infiltration and lung epithelial changes, in turn leading to a chronic inflammatory state with increased mucus production and decreased lung function. We used this model to investigate the effects of IL-17 activity on airway epithelium and identified CXCL5 and MIP-2 as important factors in neutrophil recruitment. The neutralization of IL-17 greatly reduces pulmonary neutrophilia, underscoring a key role for IL-17 in promoting chronic airway inflammation. These findings emphasize the role of IL-17 in mediating neutrophil-driven pulmonary inflammation and highlight a new mouse model that may be used for the development of novel therapies targeting Th17 cells in asthma and other chronic pulmonary diseases. |
