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Published on: August 27, 2019
Blocking mTOR Signalling with Rapamycin Ameliorates Imiquimod-induced Psoriasis in Mice
Claudia Bürger1, Nitesh Shirsath, Victoria Lang
1Department of Dermatology, Venereology and Allergy, Clinic of the Goethe-University, Theodor-Stern-Kai 7, DE-60590 Frankfurt am Main, Germany. Claudia.Buerger@kgu.de.
Abstract:
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.
Insights
Topical rapamycin, an mTOR inhibitor, reduced psoriasis severity in a mouse model. It normalized skin cell markers and decreased immune cell activation, suggesting a new treatment approach.
Area of Science:
- Dermatology
- Immunology
- Molecular Biology
Background:
- The mechanistic target of rapamycin (mTOR) pathway is hyperactivated in psoriatic skin lesions.
- This hyperactivation may impair keratinocyte maturation, contributing to psoriasis pathogenesis.
- Systemic rapamycin has shown limited therapeutic success for psoriasis.
Purpose of the Study:
- To investigate the efficacy of topical rapamycin in an imiquimod-induced mouse model of psoriasis.
- To evaluate the impact of topical rapamycin on mTOR signaling and epidermal differentiation in psoriatic skin.
Main Methods:
- An imiquimod-induced psoriasis mouse model was used.
- Mice were treated with topical rapamycin.
- Immunohistological analysis assessed mTOR signaling (P-mTOR, P-S6), epidermal differentiation markers, and immune cell infiltration.
Main Results:
- Topical rapamycin treatment significantly reduced psoriasis severity in the mouse model.
- Rapamycin inhibited mTOR signaling and normalized epidermal differentiation markers.
- A partial reduction in innate immune cell influx into lymph nodes was observed.
Conclusions:
- mTOR signaling plays a critical role in psoriasis pathogenesis.
- Topical rapamycin demonstrates potential as a novel therapeutic strategy for psoriasis.
- Targeting mTOR with topical application warrants further investigation for anti-psoriatic effects.
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