Mammalian target of rapamycin and its downstream signalling components are activated in psoriatic skin

BackgroundMammalian target of rapamycin (mTOR) signalling integrates signals leading to cellular growth, proliferation and differentiation. Disturbance of this tightly regulated interplay leads to malignancies, as reflected by altered mTOR signalling in epidermal tumours. As psoriatic keratinocytes also show features of perturbed cell growth and differentiation, the question arises as to whether mTOR signalling also plays a role in the pathogenesis of psoriasis. ObjectivesTo investigate the activation status of mTOR signalling components in psoriasis. MethodsBiopsies from lesional and nonlesional skin of patients with psoriasis (n=10), as well as samples from healthy donors (n=3), were analysed by immunohistochemistry and Western blot, utilizing antibodies detecting phosphorylated mTOR, phospho-S6 kinase and phospho-S6 ribosomal protein. ResultsWe found mTOR and its downstream signalling molecule, the ribosomal protein S6, to be activated in lesional psoriatic skin. While mTOR is activated throughout the whole epidermis, with particularly strong activation in the basal layer, S6 is active in suprabasal layers of differentiating keratinocytes. ConclusionsAltogether these results suggest a role for mTOR signalling in the epidermal changes leading to the psoriatic phenotype. mTOR inhibition might be a mode of action to explore in developing innovative antipsoriatic drugs.