Cutaneous barrier dysfunction in allergic diseases.

ABSTRACT: The fundamental defect(s) that drives atopic dermatitis (AD) remains controversial. "Outside in" proponents point to the important association of filaggrin gene mutations and other skin barrier defects with AD. The "inside out" proponents derive support from evidence that AD occurs in genetic animal models with overexpression of type 2 immune pathways in their skin, and humans with gain-of-function mutations in their type 2 response develop severe AD. The observation that therapeutic biologics, targeting type 2 immune responses, can reverse AD provides compelling support for the importance of "inside out" mechanisms of AD. In this review, we propose a central role for epithelial cell dysfunction that accounts for the dual role of skin barrier defects and immune pathway activation in AD. Th

SUBMITTER: Leung DYM 

PROVIDER: S-EPMC7291847 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature