Blocking mTOR signalling with rapamycin ameliorates imiquimod-induced psoriasis in mice
- The mTOR (mechanistic target of rapamycin) inhibitor rapamycin has long been known for its immune suppressive properties, but it has shown limited therapeutic success when given systemically to patients with psoriasis. Recent data have shown that the mTOR pathway is hyperactivated in lesional psoriatic skin, which probably contributes to the disease by interfering with maturation of keratinocytes. This study investigated the effect of topical rapamycin treatment in an imiquimod-induced psoriatic mouse model. The disease was less severe if the mice had received rapamycin treatment. Immunohistological analysis revealed that rapamycin not only prevented the activation of mTOR signalling (P-mTOR and P-S6 levels), but almost normalized the expression of epidermal differentiation markers. In addition, the influx of innate immune cells into the draining lymph nodes was partially reduced by rapamycin treatment. These data emphasize the role of mTOR signalling in the pathogenesis of psoriasis, and support the investigation of topical mTOR inhibition as a novel anti-psoriatic strategy.
Author: | Claudia BürgerORCiDGND, Nitesh Shirsath, Victoria Lang, Sandra DiehlORCiD, Roland KaufmannGND, Andreas WeigertORCiDGND, Ying-ying Han, Christian Ringel, Peter Wolf |
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URN: | urn:nbn:de:hebis:30:3-450697 |
DOI: | https://doi.org/10.2340/00015555-2724 |
ISSN: | 1651-2057 |
ISSN: | 0001-5555 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/28597024 |
Parent Title (English): | Acta dermato-venereologica |
Publisher: | Acta Dermato-Venereologica |
Place of publication: | Uppsala |
Document Type: | Article |
Language: | English |
Year of Completion: | 2017 |
Date of first Publication: | 2017/06/09 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2018/01/02 |
Tag: | imiquimod; mTORC; psoriasis; rapamycin |
Volume: | 97 |
Issue: | 9 |
Page Number: | 8 |
First Page: | 1087 |
Last Page: | 1094 |
Note: | This is an open access article under the CC BY-NC license |
HeBIS-PPN: | 451939034 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (English): | Creative Commons - Namensnennung-Nicht kommerziell 4.0 |