Abstract

Rosacea is a common inflammatory skin disorder mediated by the dysregulation of both keratinocytes and T cells. Here, we report that aquaporin 3 (AQP3), a channel protein that mediates the transport of water/glycerol, was highly expressed in the epidermis and CD4+ T cells of both rosacea patients and experimental mice. Specifically, AQP3 deletion blocked the development of rosacea-like skin inflammation in model mice with LL37-induced rosacea-like disease. We also present mechanistic evidence showing that AQP3 was essential to the activation of NF-κB signaling and subsequent production of disease-characteristic chemokines in keratinocytes. Moreover, we show that AQP3 was upregulated during T cell differentiation and promotes helper T (Th) 17 differentiation possibly via the activation of STAT3 signaling. Our findings reveal that AQP3-mediated activation of NF-κB in keratinocytes and activation of STAT3 in CD4+ T cells acted synergistically and contributed to the inflammation in rosacea.