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. R
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.
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Author:Claudia Bürger, Nitesh Shirsath, Victoria Lang, Sandra Diehl, Roland Kaufmann, Andreas Weigert, Ying-ying Han, Christian Ringel, Peter Wolf
URN:urn:nbn:de:hebis:30:3-450697
DOI:http://dx.doi.org/10.2340/00015555-2724
ISSN:1651-2057
ISSN:0001-5555
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=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
Pagenumber: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
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (English):License LogoCreative Commons - Namensnennung-Nicht kommerziell 4.0

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