IL-4 regulates skin homeostasis and the predisposition towards allergic skin inflammation 1

IL-4 promotes the development of Th2 cells and allergic inflammation. In Atopic Dermatitis (AD) lesions, IL-4 decreases the expression of multiple genes associated with innate defense including genes in the epidermal differentiation complex (EDC) that regulate epidermal barrier function. However, it is not clear whether IL-4 also contributes to homeostatic control of EDC genes. In this report we demonstrate that expression of EDC genes and barrier function is increased in the absence of endogenous IL-4. Mice that express a constitutively active Stat6 (Stat6VT) are prone to the development of allergic skin inflammation, and have decreased expression of EDC genes. IL-4-deficiency protects Stat6VT transgenic mice from the development of allergic skin inflammation and decreased recovery time in barrier function following skin irritation, with a concomitant increase in EDC gene expression. These data suggest that IL-4 plays an important role in regulating epidermal homeostasis and innate barrier function.