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

Academic Article
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Overview

authors

  • Fogli, L. K.
  • Sundrud, Mark
  • 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.

publication date

  • November 2013

journal

  • Journal of Immunology  Journal

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.

subject areas

  • Animals
  • Asthma
  • Cell Separation
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Immune System Diseases
  • Interleukin-17
  • Leukocyte Disorders
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils
  • Pneumonia
  • Real-Time Polymerase Chain Reaction
  • Respiratory Mucosa
  • Th17 Cells
  • Transfection
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Identity

PubMed Central ID

  • PMC3822005

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1301360

PubMed ID

  • 23966625
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Additional Document Info

start page

  • 3100

end page

  • 3111

volume

  • 191

issue

  • 6

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