1. T Cell–Derived IL-17 Mediates Epithelial Changes in the Airway and Drives Pulmonary Neutrophilia
- Author
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Laura K, Fogli, Mark S, Sundrud, Swati, Goel, Sofia, Bajwa, Kari, Jensen, Emmanuel, Derudder, Amy, Sun, Maryaline, Coffre, Catherine, Uyttenhove, Jacques, Van Snick, Marc, Schmidt-Supprian, Anjana, Rao, Gabriele, Grunig, Joan, Durbin, Stefano, Casola, Stefano S, Casola, Klaus, Rajewsky, and Sergei B, Koralov
- Subjects
Neutrophils ,medicine.medical_treatment ,T cell ,Immunology ,Enzyme-Linked Immunosorbent Assay ,Inflammation ,Cell Separation ,Respiratory Mucosa ,Biology ,Real-Time Polymerase Chain Reaction ,Transfection ,Article ,Proinflammatory cytokine ,Mice ,medicine ,Animals ,Immunology and Allergy ,Lung ,Interleukin-17 ,Pneumonia ,respiratory system ,Flow Cytometry ,Asthma ,Neutrophilia ,respiratory tract diseases ,Mice, Inbred C57BL ,Disease Models, Animal ,medicine.anatomical_structure ,Cytokine ,Immune System Diseases ,Th17 Cells ,Respiratory epithelium ,Interleukin 17 ,medicine.symptom ,Leukocyte Disorders - 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.
- Published
- 2013
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