Atopic dermatitis and cathepsin E

Abstract

Cathepsin E is an intracellular aspartic proteinase expressed predominantly in immune cells and skin. We show that cathepsin E-deficient mice spontaneously develop atopic dermatitis (AD)-like skin lesions comparable to human AD when kept under conventional circumstances, but not under specific pathogen-free conditions. These mice displayed AD-associated phenotypes including eosinophilia; increased serum IgE, IL-18, and IL-1β; and enhanced production of Th2 cytokines. Cathepsin E deficiency also resulted in greater decrease of the rate of degradation for serum IL-18 and IL-1β. Interestingly, cathepsin E levels in blood cells were significantly decreased in AD patients and the AD model NC/Nga mice compared to healthy donors and the control mice, respectively. Our results indicate that deficiency or defective production of cathepsin E strongly induces AD in humans and mice, probably due to the systemic accumulation of IL-18 and IL-1β, leading to stimulation of Th2 responses, and that cathepsin E-deficient mice are a newly discovered model to analyze pathologic mechanisms of human AD.