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

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Item Type:	Article
Title:	T cell-derived IL-17 mediates epithelial changes in the airway and drives pulmonary neutrophilia
Creators Name:	Fogli, L.K., Sundrud, M.S., Goel, S., Bajwa, S., Jensen, K., Derudder, E., Sun, A., Coffre, M., Uyttenhove, C., Van Snick, J., Schmidt-Supprian, M., Rao, A., Grunig, G., Durbin, J., Casola, S.S., Rajewsky, K. and Koralov, S.B.
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.
Keywords:	Animal Disease Models, Asthma, Cell Separation, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Immune System Diseases, Interleukin-17, Leukocyte Disorders, Neutrophils, Pneumonia, Real-Time Polymerase Chain Reaction, Respiratory Mucosa, Th17 Cells, Transfection, Animals, Mice
Source:	Journal of Immunology
ISSN:	0022-1767
Publisher:	American Association of Immunologists
Volume:	191
Number:	6
Page Range:	3100-3111
Date:	15 September 2013
Additional Information:	Erratum in: J Immunol 191(10): 5318.
Official Publication:	https://doi.org/10.4049/jimmunol.1301360
PubMed:	View item in PubMed

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