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The tumor necrosis factor family member LIGHT is a target for asthmatic airway remodeling
Open accessAbstract
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 β receptor (LTβR) 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-β (TGF-β) 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.
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Cites
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Johnson, J. R., Wiley, R. E., Fattouh, R., Swirski, F. K., Gajewska, B. U., Coyle, A. J., Gutierrez-Ramos, J.-C., Ellis, R., Inman, M. D., & Jordana, M. (2004) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200308-1094oc · Cited by 435
Potential action of IL-4 and IL-13 as fibrogenic factors on lung fibroblasts in vitro
Saito, A., Okazaki, H., Sugawara, I., Yamamoto, K., & Takizawa, H. (2003) · International Archives of Allergy and Immunology · doi:10.1159/000073718 · Cited by 167
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Metadata
- Authors
- Doherty, T. A., Soroosh, P., Khorram, N., Fukuyama, S., Rosenthal, P., Cho, J. Y., Norris, P. S., Choi, H., Scheu, S., Pfeffer, K., Zuraw, B. L., Ware, C. F., Broide, D. H., & Croft, M.
- Venue
- Nature Medicine
- Published
- 2011-04-17
- Volume
- 17
- Issue
- 5
- Pages
- 596-603
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2136830681
- Cited by
- 171
- References
- 2
- FWCI
- 11.75
- Type
- journal article
- Language
- en
- Open access
- green
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