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Review
. 2008 Jun;121(6):1337-43.
doi: 10.1016/j.jaci.2008.01.022. Epub 2008 Mar 7.

Basis for the barrier abnormality in atopic dermatitis: outside-inside-outside pathogenic mechanisms

Peter M Elias  1 , Yutaka Hatano, Mary L Williams
Affiliations
Review

Basis for the barrier abnormality in atopic dermatitis: outside-inside-outside pathogenic mechanisms

Peter M Elias et al. J Allergy Clin Immunol. 2008 Jun.

Abstract

Until quite recently, the pathogenesis of atopic dermatitis (AD) has been attributed to primary abnormalities of the immune system. Intensive study revealed the key roles played by T(H)1/T(H)2 cell dysregulation, IgE production, mast cell hyperactivity, and dendritic cell signaling in the evolution of the chronic, pruritic, inflammatory dermatosis that characterizes AD. Accordingly, current therapy has been largely directed toward ameliorating T(H)2-mediated inflammation and pruritus. In this review we will assess emerging evidence that inflammation in AD results from inherited and acquired insults to the barrier and the therapeutic implications of this paradigm.

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Conflict of interest statement

Disclosure of potential conflict of interest: P. M. Elias has served as a member for Ceragenix and has served as an expert witness in immunomodification and systemic retinoid litigation. M. L. Williams’ husband has served as a member of Ceragenix. Y. Hatano has declared that he has no conflict of interest.

Figures

FIG 1
FIG 1
Inherited and acquired activation of serine proteases converge to affect multiple SC functions but by divergent mechanisms. SPI, Serine protease inhibitor; DSG1, desmoglein 1; CD, corneodesmosome; LEKTI, lymphoepithelial Kazal-type trypsin inhibitor; PAR2, plasminogen activator type 2 receptor;KLK7, kallikrein 7.
FIG 2
FIG 2
FLG proteolytic pathway affects multiple SC functions: potential implications for pathogenesis of AD. R.H., Relative humidity; trans-UCA, trans-urocanic acid.
FIG 3
FIG 3
Outside-inside initial provocation of AD eventually can lead to an outside-inside-outside vicious cycle. hBD2, Human β-defensin; AR, amphiregulin; NGF, nerve growth factor.
FIG 4
FIG 4
Role of secondary infections in further aggravation of AD. AMP, Antimicrobial peptides; FFA, free fatty acids.
See this image and copyright information in PMC

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