The tumor necrosis factor family member LIGHT is a target for asthmatic airway remodeling

被引：142

作者：

Doherty, Taylor A. ^{[1
,2
]}

Soroosh, Pejman ^{[1
]}

Khorram, Naseem ^{[2
]}

Fukuyama, Satoshi ^{[1
]}

Rosenthal, Peter ^{[2
]}

Cho, Jae Youn ^{[2
]}

Norris, Paula S. ^{[3
]}

Choi, Heonsik ^{[1
]}

Scheu, Stefanie ^{[4
]}

Pfeffer, Klaus ^{[4
]}

Zuraw, Bruce L. ^{[2
]}

Ware, Carl F. ^{[3
]}

Broide, David H. ^{[2
]}

Croft, Michael ^{[1
]}

机构：

[1] La Jolla Inst Allergy & Immunol, Div Immune Regulat, La Jolla, CA USA

[2] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

[3] Sanford Burnham Med Res Inst, Infect & Inflammatory Dis Ctr, La Jolla, CA USA

[4] Univ Dusseldorf, Inst Med Microbiol, Dusseldorf, Germany

来源：

NATURE MEDICINE | 2011年 / 17卷 / 05期

基金：

美国国家卫生研究院;

关键词：

GROWTH-FACTOR-BETA; T-CELL-ACTIVATION; TGF-BETA; LYMPHOTOXIN-BETA; BASEMENT-MEMBRANE; EPITHELIAL-CELLS; TNF SUPERFAMILY; INFLAMMATION; EXPRESSION; RECEPTOR;

D O I：

10.1038/nm.2356

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Individuals with chronic asthma show a progressive decline in lung function that is thought to be due to structural remodeling of the airways characterized by subepithelial fibrosis and smooth muscle hyperplasia. Here we show that the tumor necrosis factor (TNF) family member LIGHT is expressed on lung inflammatory cells after allergen exposure. Pharmacological inhibition of LIGHT using a fusion protein between the IgG Fc domain and lymphotoxin beta receptor (LT beta R) reduces lung fibrosis, smooth muscle hyperplasia and airway hyperresponsiveness in mouse models of chronic asthma, despite having little effect on airway eosinophilia. LIGHT-deficient mice also show a similar impairment in fibrosis and smooth muscle accumulation. Blockade of LIGHT suppresses expression of lung transforming growth factor-beta (TGF-beta) and interleukin-13 (IL-13), cytokines implicated in remodeling in humans, whereas exogenous administration of LIGHT to the airways induces fibrosis and smooth muscle hyperplasia, Thus, LIGHT may be targeted to prevent asthma-related airway remodeling.

引用

页码：596 / U118

页数：9

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