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- Title
An alternative pathway of imiquimod-induced psoriasis-like skin inflammation in the absence of interleukin-17 receptor a signaling.
- Authors
El Malki, Khalifa; Karbach, Susanne H; Huppert, Jula; Zayoud, Morad; Reissig, Sonja; Schüler, Rebecca; Nikolaev, Alexej; Karram, Khalad; Münzel, Thomas; Kuhlmann, Christoph R W; Luhmann, Heiko J; von Stebut, Esther; Wörtge, Simone; Kurschus, Florian C; Waisman, Ari
- Abstract
Topical application of imiquimod (IMQ) on the skin of mice induces inflammation with common features found in psoriatic skin. Recently, it was postulated that IL-17 has an important role both in psoriasis and in the IMQ model. To further investigate the impact of IL-17RA signaling in psoriasis, we generated IL-17 receptor A (IL-17RA)-deficient mice (IL-17RA(del)) and challenged these mice with IMQ. Interestingly, the disease was only partially reduced and delayed but not abolished when compared with controls. In the absence of IL-17RA, we found persisting signs of inflammation such as neutrophil and macrophage infiltration within the skin. Surprisingly, already in the naive state, the skin of IL-17RA(del) mice contained significantly elevated numbers of Th17- and IL-17-producing γδ T cells, assuming that IL-17RA signaling regulates the population size of Th17 and γδ T cells. Upon IMQ treatment of IL-17RA(del) mice, these cells secreted elevated amounts of tumor necrosis factor-α, IL-6, and IL-22, accompanied by increased levels of the chemokine CXCL2, suggesting an alternative pathway of neutrophil and macrophage skin infiltration. Hence, our findings have major implications in the potential long-term treatment of psoriasis by IL-17-targeting drugs.
- Publication
The Journal of investigative dermatology, 2013, Vol 133, Issue 2, p441
- ISSN
1523-1747
- Publication type
Journal Article
- DOI
10.1038/jid.2012.318