Eosinophils Determine Dermal Thickening and Water Loss in an MC903 Model of Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a highly debilitating disease with significant health impacts worldwide. It has been a difficult disease to treat because of the wide spectrum of clinical manifestations. Therefore, the current clinical management strategies are nonspecific. Previous studies have documented that AD disease progression is precipitated by a combination of skin barrier dysfunction, itch, and immune dysregulation. However, the precise roles played by effector cells and cytokines have not been fully elucidated. To address this, we established a prolonged model of AD, using MC903. The phenotype of this MC903 model closely resembles the one observed in AD patients, including inflammatory parameters, barrier dysfunction, itch, and histopathological characteristics, thereby providing a platform to evaluate targets for the treatment of AD. This model exposed cells and cytokines that are critically associated with disease severity, including eosinophils, TSLP, and IL-4/IL-13. Indeed, eosinophil depletion significantly ameliorated AD pathology, most notably barrier dysfunction, to a similar extent as blocking of the IL-4/IL-13 axis by genetic deletion of STAT6. Thus, this study has identified eosinophils to be critical for the development and maintenance of AD, thereby proposing these effector cells as therapeutic targets for the treatment of AD.