Claudin-3 in Sweat Glands Prevents the Leakage of Sweat

Sweat has been found to be involved in aggravation of atopic dermatitis (AD) symptoms in diverse ways. Previous reports pointed out the leakage of sweat from sweat glands into the dermis. Furthermore, subsequent decreases in the amount of sweat can exacerbate symptoms via skin dryness and elevated temperature. However, research has not yet shown how sweat leak from sweat glands in AD. To tackle this issue, we investigated the impact of tight junctions on preventing the leakage of sweat. Human skin specimens were immunohistochemically stained for Claudins and Dermacidin. Moreover, the abilities of sweat secretion were evaluated in Claudin-3 knockout (KO) mice by counting the number of active sweat pores with a starch-iodine reaction and by observing the kinetics of sweat secretion with optical coherence tomography. In humans, Claudin-3 was abundantly expressed in both the sweat duct and the secretory coil, while Claudin-1 was expressed only in the sweat duct. Skin specimens derived from AD patients showed the decreased expression of Claudin-1 and -3 in the sweat duct. Dermacidin was clearly detected around the sweat glands in these patients, indicating the leakage of sweat into the dermis. In mice, Claudin-3 was abundant in sweat glands, as in humans, while Claudin-1 was not expressed. Evaluation of the kinetics of sweat secretion revealed the reduced sweat secretion in Claudin-3 KO mice. Furthermore, the observation of tracing sweat-flow in Claudin-3 KO mice revealed that fluorescent tracer leaked into the paracellular space of the sweat duct. In conclusion, our findings indicate that Claudin-3 in sweat glands prevents the leakage of sweat. The knowledge gained in this study will contribute to formulating guidance for AD patients for the management of sweat.