The key role of Aquaporin 3 and Aquaporin 10 in the pathogenesis of pompholyx (P6372)

Abstract

Abstract Pompholyx (a.k.a dyshidrotic eczema) is a skin affliction without a compelling pathophysiological trigger. The disease is characterized by the sudden onset of blisters exclusively in the hands and soles that can expand and fuse, eventually leading to heavily dehydrated skin. Using immunofluorescence we found that the aquaglyceroporins Aquaporin 3 (AQP3) and Aquaporin-10 (AQP10) are aberrantly expressed across the suprabasal keratinocytes in the involved palm lesions of pompholyx patients compared to uninvolved skin and skin from healthy controls. AQP3 and AQP10 function as bi-directional transport channels for water and glycerol, and their activity is inhibited at acidic pH and favored at basic pH. The suprabasal keratinocyte presence of these two aquaglyceroporins may bridge the abundantly hydrated dermis and basal epidermis to the outer environment in pompholyx, creating a dehydrating osmotic gradient imbalance as a result from exposure to exogenous water. Since hands are typically exposed to water numerous times daily, this constant osmotic gradient imbalance may provide a mechanistic explanation for the extreme dehydration observed clinically in pompholyx skin patients, thus irreversibly altering the skin homeostasis and contributing to the chronic cutaneous inflammation of this disease.