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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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Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling
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
Cited by
TGF-β1 Signaling and Tissue Fibrosis
Kim, K. K., Sheppard, D., & Chapman, H. A. (2018) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a022293 · Cited by 800
The TNF Receptor Superfamily in Co-stimulating and Co-inhibitory Responses
Ward-Kavanagh, L. K., Lin, W. W., Šedý, J. R., & Ware, C. F. (2016) · Immunity · doi:10.1016/j.immuni.2016.04.019 · Cited by 463
Self-citationMacrophages of distinct origins contribute to tumor development in the lung
Loyher, P.-L., Hamon, P., Laviron, M., Meghraoui-Kheddar, A., Goncalves, E., Deng, Z., Torstensson, S., Bercovici, N., Baudesson de Chanville, C., Combadière, B., et al. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20180534 · Cited by 298
Therapies for allergic inflammation: refining strategies to induce tolerance
Akdis, C. A. (2012) · Nature Medicine · doi:10.1038/nm.2754 · Cited by 296
Srinivasan, M., Flynn, R., Price, A., Ranger, A., Browning, J. L., Taylor, P. A., Ritz, J., Antin, J. H., Murphy, W. J., Luznik, L., et al. (2012) · Blood · doi:10.1182/blood-2011-07-364414 · Cited by 260
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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- 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. (2011). The tumor necrosis factor family member LIGHT is a target for asthmatic airway remodeling. Nature Medicine. https://doi.org/10.1038/nm.2356
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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