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Dual inhibition of TNFR1 and IFNAR1 in imiquimod-induced psoriasiform skin inflammation in mice

Lynda Grine (UGent) , Lien Dejager (UGent) , Claude Libert (UGent) and Roosmarijn Vandenbroucke (UGent)
(2015) JOURNAL OF IMMUNOLOGY. 194(11). p.5094-5102
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Abstract
Psoriasis is a chronic inflammatory skin disease affecting 2-3% of the world population and is mainly characterized by epidermal hyperplasia, scaling, and erythema. A prominent role for TNF in the pathogenesis of psoriasis has been shown, and consequently various types of TNF antagonists such as etanercept and infliximab have been used successfully. Recently, increasing amounts of data suggest that type I IFNs are also crucial mediators of psoriasis. To investigate whether blocking their respective receptors would be useful, TNFR1-and IFNAR1-deficient mice were challenged with Aldara, which contains imiquimod, and is used as an experimental model to induce psoriasis-like skin lesions in mice. Both transgenic mice showed partial protection toward Aldarainduced inflammation compared with control groups. Additionally, TNFR1 knockout mice showed sustained type I IFN production in response to Aldara. Double knockout mice lacking both receptors showed superior protection to Aldara in comparison with the single knockout mice and displayed reduced levels of IL-12p40, IL-17F, and S100A8, indicating that the TNF and type I IFN pathways contribute significantly to inflammation upon treatment with Aldara. Our findings reveal that dual inhibition of TNFR1 and IFNAR1 may represent a potential novel strategic treatment of psoriasis.
Keywords
NECROSIS-FACTOR-ALPHA, INTERFERON REGULATORY FACTOR-3, SYSTEMIC-LUPUS-ERYTHEMATOSUS, ACTIVE CROHNS-DISEASE, FACTOR RECEPTOR 1, DELTA T-CELLS, RHEUMATOID-ARTHRITIS, I INTERFERON, AUTOIMMUNE-DISEASES, PSORIATIC SKIN

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Chicago
GRINE, LYNDA, Lien Dejager, Claude Libert, and Roosmarijn Vandenbroucke. 2015. “Dual Inhibition of TNFR1 and IFNAR1 in Imiquimod-induced Psoriasiform Skin Inflammation in Mice.” Journal of Immunology 194 (11): 5094–5102.
APA
GRINE, L., Dejager, L., Libert, C., & Vandenbroucke, R. (2015). Dual inhibition of TNFR1 and IFNAR1 in imiquimod-induced psoriasiform skin inflammation in mice. JOURNAL OF IMMUNOLOGY, 194(11), 5094–5102.
Vancouver
1.
GRINE L, Dejager L, Libert C, Vandenbroucke R. Dual inhibition of TNFR1 and IFNAR1 in imiquimod-induced psoriasiform skin inflammation in mice. JOURNAL OF IMMUNOLOGY. 2015;194(11):5094–102.
MLA
GRINE, LYNDA, Lien Dejager, Claude Libert, et al. “Dual Inhibition of TNFR1 and IFNAR1 in Imiquimod-induced Psoriasiform Skin Inflammation in Mice.” JOURNAL OF IMMUNOLOGY 194.11 (2015): 5094–5102. Print.
@article{6888333,
  abstract     = {Psoriasis is a chronic inflammatory skin disease affecting 2-3\% of the world population and is mainly characterized by epidermal hyperplasia, scaling, and erythema. A prominent role for TNF in the pathogenesis of psoriasis has been shown, and consequently various types of TNF antagonists such as etanercept and infliximab have been used successfully. Recently, increasing amounts of data suggest that type I IFNs are also crucial mediators of psoriasis. To investigate whether blocking their respective receptors would be useful, TNFR1-and IFNAR1-deficient mice were challenged with Aldara, which contains imiquimod, and is used as an experimental model to induce psoriasis-like skin lesions in mice. Both transgenic mice showed partial protection toward Aldarainduced inflammation compared with control groups. Additionally, TNFR1 knockout mice showed sustained type I IFN production in response to Aldara. Double knockout mice lacking both receptors showed superior protection to Aldara in comparison with the single knockout mice and displayed reduced levels of IL-12p40, IL-17F, and S100A8, indicating that the TNF and type I IFN pathways contribute significantly to inflammation upon treatment with Aldara. Our findings reveal that dual inhibition of TNFR1 and IFNAR1 may represent a potential novel strategic treatment of psoriasis.},
  author       = {Grine, Lynda and Dejager, Lien and Libert, Claude and Vandenbroucke, Roosmarijn},
  issn         = {0022-1767},
  journal      = {JOURNAL OF IMMUNOLOGY},
  language     = {eng},
  number       = {11},
  pages        = {5094--5102},
  title        = {Dual inhibition of TNFR1 and IFNAR1 in imiquimod-induced psoriasiform skin inflammation in mice},
  url          = {http://dx.doi.org/10.4049/jimmunol.1403015},
  volume       = {194},
  year         = {2015},
}

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