title: T cell-derived IL-17 mediates epithelial changes in the airway and drives pulmonary neutrophilia.
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.
authors: Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
authors: Laura K
authors: LK
authors: Fogli
authors: Mark S
authors: MS
authors: Sundrud
authors: Swati
authors: S
authors: Goel
authors: Sofia
authors: S
authors: Bajwa
authors: Kari
authors: K
authors: Jensen
authors: Emmanuel
authors: E
authors: Derudder
authors: Amy
authors: A
authors: Sun
authors: Maryaline
authors: M
authors: Coffre
authors: Catherine
authors: C
authors: Uyttenhove
authors: Jacques
authors: J
authors: Van Snick
authors: Marc
authors: M
authors: Schmidt-Supprian
authors: Anjana
authors: A
authors: Rao
authors: Gabriele
authors: G
authors: Grunig
authors: Joan
authors: J
authors: Durbin
authors: Stefano
authors: S
authors: Casola
authors: Stefano S
authors: SS
authors: Casola
authors: Klaus
authors: K
authors: Rajewsky
authors: Sergei B
authors: SB
authors: Koralov
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007154:Immune System Diseases / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D007960:Leukocyte Disorders / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology*; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D014162:Transfection
chemical_list: D020381:Interleukin-17
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