Atopic dermatitis (AD), a common manifestation of allergic disease, can be an early indicator of subsequent atopic phenotypes. Mutations in the Filaggrin gene, a component of the Epidermal Differentiation Complex (EDC) has emerged as a predisposing factor for the development of AD. EDC genes are critical for barrier function in the skin, but the Th2-type cytokines IL-4 and IL-13 inhibit expression of EDC genes in keratinocytes. We hypothesized that pro-allergic cytokines alter skin barrier function and facilitate allergen exposure by altering keratinocyte differentiation. Thus, to define the mechanisms of IL-4-dependent changes in gene expression, the activation of STAT6 was investigated in normal human keratinocytes (HK). We observed that STAT6+ cells were induced by IL-4, resulting in a peak of positive cells after 30 minutes of stimulation. Moreover, IL-4 significantly inhibited EDC genes expression in HK differentiated in vitro. IL-4 also resulted in a significant increase in the expression of the chemokine CCL26 (Eotaxin3) and the matricellular protein periostin, which is involved in persistent allergic inflammation. Thus, IL-4-dependent changes in keratinocyte gene expression are likely a key component in AD pathogenesis.
- Copyright © 2013 by The American Association of Immunologists, Inc.