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

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 S. Casola, Klaus Rajewsky, Sergei B. Koralov

Research output: Contribution to journalArticle

55 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3100-3111
Number of pages12
JournalJournal of Immunology
Volume191
Issue number6
DOIs
StatePublished - Sep 15 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    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., & Koralov, S. B. (2013). T cell-derived IL-17 mediates epithelial changes in the airway and drives pulmonary neutrophilia. Journal of Immunology, 191(6), 3100-3111. https://doi.org/10.4049/jimmunol.1301360