Epidermis-Specific Ablation of Claudin-1 in Adult Mice Demonstrates the Essential Role of a Tight Junction Barrier in Skin Homeostasis

The study demonstrated that epidermis-specific ablation of claudin-1 in adult mice led to significant skin barrier defects and inflammation. Claudin-1 knockout mice showed a progressive loss of claudin-1 staining, starting from the basal and spinous layers and extending to the granular layers by day 8, resulting in tight junction (TJ) barrier leakage and activation of Langerhans cells (LCs). By day 18, the mice exhibited compact hyperkeratosis, increased water evaporation through isolated SC sheets (WETIS), elevated trans-epidermal water loss (TEWL), erythema, scales, abnormal sebum secretion, partial hair loss, and scratching behaviors. These results indicated that TJ barrier leakage could induce stratum corneum (SC) barrier defects and skin inflammation, highlighting the critical role of TJs in maintaining skin homeostasis and providing insights into the pathophysiology of atopic dermatitis.