Skin barrier function

Abstract

Like other inflammatory dermatoses, the pathogenesis of atopic dermatitis (AD) has been largely attributed to abnormalities in adaptive immunity. T helper (Th) cell types 1 and 2 cell dysregulation, IgE production, mast cell hyperactivity, and dendritic cell signaling are thought to account for the chronic, pruritic, and inflammatory dermatosis that characterizes AD. Not surprisingly, therapy has been directed toward ameliorating Th2-mediated inflammation and pruritus. Here, we review emerging evidence that inflammation in AD occurs downstream to inherited and acquired insults to the barrier. Therapy based upon this new view of pathogenesis should emphasize approaches that correct the primary abnormality in barrier function, which drives downstream inflammation and allows unrestricted antigen access.

Figure 1

Pathogen colonization further aggravates the barrier abnormality in atopic dermatitis (AD). AMP—antimicrobial peptides; Cer—ceramides; FLG—filaggrin; LEKTI—lymphoepithelial Kazal-type trypsin inhibitor; PS—psychologic stress; RH—relative humidity; Th1—T helper cell type 1; Th2—T helper cell type 2.

Figure 2

Outside-inside initial provocation could be followed by back-to-outside vicious cycle. Cer—ceramide; FLG—filaggrin; hBD2—human β-defensins; Th2—T helper cell type 2.