title: New concept of the pathogenesis of atopic dermatitis: interplay among the barrier, allergy, and pruritus as a trinity.
abstract: Atopic dermatitis (AD) is a common skin condition, characterized by a complex, heterogeneous pathogenesis, including skin barrier dysfunctions, allergy/immunology, and pruritus. When the skin barrier is disrupted by, for example, the filaggrin gene mutation and/or environmental factors, the skin is predisposed to being penetrated by external stimuli. Foreign antigens can be subdivided into two subsets by size: haptens (including metals) and protein antigens. It is known that a single hapten challenge provokes Th1 initially, but that repeated elicitation with haptens results in a shift toward Th2-dominated responses. On the other hand, exposure to protein antigens directly induces Th2-dominant conditions via the thymic stromal lymphopoietin (TSLP) receptor on Langerhans cells. Recently, it has been revealed that Th2 cells produce IL-31, which provokes pruritus, and that Th2 cytokines decrease filaggrin expressions by keratinocytes. These findings suggest that Th2 conditions lead to pruritus and barrier dysfunctions. In this review, we will examine the highly complex interplay among skin barrier abnormality, allergy/immunology, and pruritus as a trinity in the development of AD.
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan. kaba@kuhp.kyoto-u.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
mesh_terms: D000818:Animals; D003876:Dermatitis, Atopic / Q000209:etiology* / Q000276:immunology*; D000091344:Filaggrin Proteins; D006241:Haptens / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007381:Intermediate Filament Proteins / Q000276:immunology; D007801:Langerhans Cells / Q000276:immunology; D011537:Pruritus / Q000276:immunology*
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D006241:Haptens; D007381:Intermediate Filament Proteins