Pathobiology of chronic inflammatory skin diseases: interplay between keratinocytes and immune cells as a target for anti-inflammatory drugs

Abstract

Inflammatory dermatoses encompass an enormous area of dermatopathology. These diseases are triggered and maintained by aberrant responses of the cells of the skin immune system. In the last decade it has become clear that epidermal keratinocytes are highly active immunological cells, with a major control over the acute and the chronic phase of skin inflammation by means of cytokine/chemokine production and surface molecule expression. In their turn, these rather disease-specific events driven by keratinocytes lead to a rich inflammatory infiltrate in the whole skin including the upper layers of the epidermis, and eventually in the aggravation and/or perpetuation of the skin disorder. Recently introduced single molecule-targeted biological drugs are offering the best demonstration that a fine definition of the molecular pathways underlying skin disorders is now necessary to identify the relevant therapeutic targets and finally obtain successful treatment of these diseases. In this review, we will summarize recent progress in our understanding of the immunologic basis of psoriasis, allergic contact dermatitis and atopic dermatitis, with special emphasis on potentially effective targets for novel anti-inflammatory drugs.