T cell–derived IL-17 mediates epithelial changes in the airway and drives pulmonary neutrophilia

LK Fogli, MS Sundrud, S Goel, S Bajwa… - The journal of …, 2013 - journals.aai.org
LK Fogli, MS Sundrud, S Goel, S Bajwa, K Jensen, E Derudder, A Sun, M Coffre…
The journal of immunology, 2013journals.aai.org
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 …
Abstract
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.
journals.aai.org