Cutaneous permeability barrier function in signal transducer and activator of transcription 6-deficient mice is superior to that in wild-type mice

Th2 cytokines exhibit a variety of inhibitory effects on permeability barrier function via signal transducer and activator of transcription 6 (STAT6). However, the role of STAT6 signaling on the construction and/or homeostasis of permeability barrier function in the physiological state has not been fully assessed. We compared permeability barrier function between Stat6-deficient and wild-type C57BL/6 mice at steady state. Measurement of transepidermal water loss and quantitative penetration assay revealed that permeability barrier function was superior in Stat6-deficient mice. Accordingly, expressions of loricrin, acidic sphingomyelinase (aSMase) and β-glucocerebrosidase (β-GlcCer’ase) in epidermis and ceramide levels in stratum corneum were elevated in STAT6-deficient mice. On the other hands, up-regulations of loricrin, aSMase and β-GlcCer’ase were not observed in 3-dimensionally cultured human keratinocytes transfected with siRNA for STAT6. Meanwhile, number of mast cells in the dermis was decreased in Stat6-deficient mice. These results suggest that STAT6 signaling negatively affects permeability barrier function in vivo, even in the physiological state. However, the superior permeability barrier function in Stat6-deficient mice may be a secondary effect exerted via cells other than keratinocytes, such as mast cells, since mast cells are known to influence permeability barrier function in vivo. Blockade of STAT6 signaling might be a strategy to augment the permeability barrier function.