期刊
JOURNAL OF IMMUNOLOGY
卷 191, 期 6, 页码 3100-3111出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1301360
关键词
-
类别
资金
- New York University Vittorio Defendi Fellowship
- GlaxoSmithKline/Immune Disease Institute
- National Institutes of Health [CA42471, AI40127, 1R01 HL095764-01]
- New York University Whitehead Fellowship
- a Feinberg Lymphoma Grant
- Concern Foundation
- Cancer Center Support Grant for Shared Resources to New York University Cancer Institute, NCI [2P30CA016087-33]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据