There is increasing evidence that autophagy contributes to the epidermal differentiation; however, the role of autophagy in epidermal tight junction (TJ) barrier remains unclear. To evaluate the role of autophagy in the maintenance of skin TJ barrier, we knocked out autophagy in human primary keratinocytes by infecting cell with autophagy-related gene 3 (Atg3) C264S mutant adenovirus. In these autophagy-deficient keratinocytes, we found that the mRNA expression and/or protein expression of TJ-related proteins such as claudin-1 and ZO-1, and the stratum corneum proteins such as filaggrin and loricrin were significantly decreased. Similarly, we observed that the transepithelial electrical resistance, a parameter for assessment of the TJ barrier function, decreased in autophagy-deficient keratinocytes. Furthermore, we established a skin-specific autophagy knockout mice (K14CreAtg7f/f mice) to clarify the role of autophagy in the maintenance of skin barrier. Interestingly, within one month postnatal, the bodyweight of K14CreAtg7f/f mice was low and the transepidermal water loss increased significantly compared to those in the wild-type mice. This observation lasted until day 40 postnatal. Notably, the junctional structure assessed with electron microscopy in the skin from autophagy-deficient mice was disrupted in K14CreAtg7f/f mice, suggesting that autophagy deficiency may result in the disruption of TJ barrier. Collectively, our findings provide evidence that autophagy activation is required for the maintenance of epidermal TJ barrier, and regulation of autophagy might be a novel therapy for the treatment of skin disorders such as atopic dermatitis characterized by defects of autophagy and skin barrier.

ESDR103 - Autophagy activation is required for the maintenance of skin tight junction barrier

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING