期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 121, 期 7, 页码 2863-2875出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI45589
关键词
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资金
- NIH [HL63993, ARRA HL090662, NS04415, AI068090, P30-DK26743, DK06414]
- Sandler SABRE award
- Burroughs Wellcome Fund
- Technical Training Foundation
- A.P Gianinni Foundation
The airway is a primary portal of entry for noxious environmental stimuli that can trigger airway remodeling, which contributes significantly to airway obstruction in chronic obstructive pulmonary disease (COPD) and chronic asthma. Important pathologic components of airway remodeling include fibrosis and abnormal innate and adaptive immune responses. The positioning of fibroblasts in interstitial spaces suggests that they could participate in both fibrosis and chemokine regulation of the trafficking of immune cells such as dendritic cells, which are crucial antigen-presenting cells. However, physiological evidence for this dual role for fibroblasts is lacking. Here, in two physiologically relevant models - conditional deletion in mouse fibroblasts of the TGF-beta-activating integrin alpha v beta 8 and neutralization of alpha v beta 8 in human COPD fibroblasts - we have elucidated a mechanism whereby lung fibroblast chemokine secretion directs dendritic cell trafficking, in a manner that is critically dependent on alpha v beta 8-mediated activation of TGF-beta by fibroblasts. Our data therefore indicate that fibroblasts have a crucial role in regulating both fibrotic and immune responses in the lung.
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