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

共 60 条

[41] Manipulation of allergen-induced airway remodeling by treatment with anti-TGF-β antibody:: Effect on the Smad signaling pathway [J].

McMillan, SJ ;

Xanthou, G ;

Lloyd, CM .

JOURNAL OF IMMUNOLOGY, 2005, 174 (09) :5774-5780

[42] Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4+ CD25-LAP+ T cells [J].

Ochi, Hirofumi ;

Abraham, Michal ;

Ishikawa, Hiroki ;

Frenkel, Dan ;

Yang, Kaiyong ;

Basso, Alexandre S. ;

Wu, Henry ;

Chen, Mei-Ling ;

Gandhi, Roopali ;

Miller, Ariel ;

Maron, Ruth ;

Weiner, Howard L. .

NATURE MEDICINE, 2006, 12 (06) :627-635

[43] Differences in airway remodeling between subjects with severe and moderate asthma [J].

Pepe, C ;

Foley, S ;

Shannon, J ;

Lemiere, C ;

Olivenstein, R ;

Ernst, P ;

Ludwig, MS ;

Martin, JG ;

Hamid, Q .

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2005, 116 (03) :544-549

[44] Potential action of IL-4 and IL-13 as fibrogenic factors on lung fibroblasts in vitro [J].

Saito, A ;

Okazaki, H ;

Sugawara, I ;

Yamamoto, K ;

Takizawa, H .

INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY, 2003, 132 (02) :168-176

[45] OX40 (CD134) controls memory T helper 2 cells that drive lung inflammation [J].

Salek-Ardakani, S ;

Song, JX ;

Halteman, BS ;

Jember, AGH ;

Akiba, H ;

Yagita, H ;

Croft, M .

JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (02) :315-324

[46] Targeted disruption of LIGHT causes defects in costimulatory T cell activation and reveals cooperation with lymphotoxin β in mesenteric lymph node genesis [J].

Scheu, S ;

Alferink, J ;

Pötzel, T ;

Barchet, W ;

Kalinke, U ;

Pfeffer, K .

JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 195 (12) :1613-1624

[47] In vivo blockade of OX40 ligand inhibits thymic stromal lymphopoietin driven atopic inflammation [J].

Seshasayee, Dhaya ;

Lee, Wyne P. ;

Zhou, Meijuan ;

Shu, Jean ;

Suto, Eric ;

Zhang, Juan ;

Diehl, Laurie ;

Austin, Cary D. ;

Meng, Y. Gloria ;

Tan, Martha ;

Bullens, Sherron L. ;

Seeber, Stefan ;

Fuentes, Maria E. ;

Labrijn, Aran F. ;

Graus, Yvo M. F. ;

Miller, Lisa A. ;

Schelegle, Edward S. ;

Hyde, Dallas M. ;

Wu, Lawren C. ;

Hymowitz, Sarah G. ;

Martin, Flavius .

JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (12) :3868-3878

[48] Components of airway hyperresponsiveness and their associations with inflammation and remodeling in mice [J].

Southam, David S. ;

Ellis, Russ ;

Wattie, Jennifer ;

Inman, Mark D. .

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2007, 119 (04) :848-854

[49] Detection and quantitation of eosinophils in the murine respiratory tract by flow cytometry [J].

Stevens, Whitney W. ;

Kim, Taeg S. ;

Pujanauski, Lindsey A. ;

Hao, Xueli ;

Braciale, Thomas J. .

JOURNAL OF IMMUNOLOGICAL METHODS, 2007, 327 (1-2) :63-74

[50] Expression of lymphotoxin-αβ on antigen-specific T cells is required for DC function [J].

Summers-deLuca, Leslie E. ;

McCarthy, Douglas D. ;

Cosovic, Bojana ;

Ward, Lesley A. ;

Lo, Calvin C. ;

Scheu, Stefanie ;

Pfeffer, Klaus ;

Gommerman, Jennifr L. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (05) :1071-1081

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