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

Summary Background Mammalian target of rapamycin (m TOR ) signalling integrates signals leading to cellular growth, proliferation and differentiation. Disturbance of this tightly regulated interplay leads to malignancies, as reflected by altered m TOR signalling in epidermal tumours. As psoriatic keratinocytes also show features of perturbed cell growth and differentiation, the question arises as to whether m TOR signalling also plays a role in the pathogenesis of psoriasis. Objectives To investigate the activation status of m TOR signalling components in psoriasis. Methods Biopsies 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 m TOR , phospho‐ S 6 kinase and phospho‐ S 6 ribosomal protein. Results We found m TOR and its downstream signalling molecule, the ribosomal protein S 6, to be activated in lesional psoriatic skin. While m TOR is activated throughout the whole epidermis, with particularly strong activation in the basal layer, S 6 is active in suprabasal layers of differentiating keratinocytes. Conclusions Altogether these results suggest a role for m TOR signalling in the epidermal changes leading to the psoriatic phenotype. m TOR inhibition might be a mode of action to explore in developing innovative antipsoriatic drugs.