Delayed onset of epidermal differentiation in psoriasis

Abstract

In normal epidermis, as previously reported, the first signs of differentiation occur within the basal layer in a subpopulation of keratinocytes that start to express K1 and K10 "supra-basal" keratin transcripts (20-30% of the basal cells) and proteins (5-10% of the basal cells). We found that in psoriatic lesions, the basal layer was devoid of cells expressing these early differentiation markers. This was already the case at the periphery of the lesions, where epidermis, although slightly acanthotic, still completes the keratinization process. In the center of the lesions, not only the basal layer, but also several rows of suprabasal cells, were negative for keratin K10 transcripts or protein. Moreover, the upper nucleated layers of involved epidermis were also devoid of K10 keratin transcripts or proteins. In normal epidermis, as previously reported, transcripts for the "basal" K5 keratin were mainly restricted to the basal layer, whereas the protein persisted in a few suprabasal layers. We found that in psoriatic epidermis, K5 keratin transcripts persisted in several suprabasal layers up to the level where K10 keratin transcripts appeared. These data, although not contradictory with previous reports showing a reduction of K1-K10 keratins and other differentiation markers in psoriasis, demonstrate that these quantitative changes are in fact the result of major qualitative differences in the distribution of these markers in psoriatic versus normal skin. Our results indicating that the onset of differentiation is delayed in psoriasis show that, contrary to conclusions accepted so far, not only the suprabasal compartment, but also the basal one, is abnormal in psoriatic epidermis.