Atopic Dermatitis and the Stratum Corneum: Part 2: Other Structural and Functional Characteristics of the Stratum Corneum Barrier in Atopic Skin

This three-part review presents what is currently known about the involvement and interdependency of the epidermal barrier and immune response in the etiopathogenesis of atopic dermatitis. Part 1 of this review depicted the role of filaggrin in atopic dermatitis while this article, Part 2, evaluates the role of serine proteases and specific lipids in the structural and functional integrity of the stratum corneum and its multiple barrier functions in atopic dermatitis. Upregulation of serine protease activity causes adverse structural changes of the stratum corneum due to degradation of certain stratum corneum proteins that are integral to epidermal structure and functions, interference with the formation of the stratum corneum intercellular lipid membrane, which normally regulates epidermal water flux and gradient, and induction of a TH2 pattern of inflammation, which is the hallmark profile of atopic skin. Alteration in lipid ratios and changes in lipid-directed enzymes may play a role in the impairment of barrier functions that are associated with atopic dermatitis. In Part 3, immune dysregulation, including upregulation of a TH2 inflammation pattern, augmented allergic sensitization, sustained wound healing inflammation, and impaired innate immunity are discussed. The roles of the stratum corneum permeability barrier, the immune defense barrier, and antimicrobial barrier in AD pathogenesis are explained in detail. With this explanation, the interdependence of the multitude of polymorphisms and dysregulations seen in AD skin will become clear. The condensing of these impaired and/or dysregulated functions and how they interact should provide further knowledge about the pathogenic mechanisms that cause atopic dermatitis, how they are clinically relevant, and how they may assist in developing more specific therapies directed at the pathogenesis of atopic dermatitis.