Olfactory dysfunction associated with atopic dermatitis in NC/Tnd mice

Atopic dermatitis (AD) is one of the intractable chronic inflammatory diseases and is often accompanied by mental disorders, such as depression. On the other hand, depression has been pointed out to be strongly associated with the onset of anosmia. However, no clinical or basic research report has been conducted on whether olfactory dysfunction develops in patients suffering from AD. Since NC/Tnd mice, a spontaneous AD model, exhibit depressive symptoms, NC/Tnd mice were used to clarify this point. We found that mice with AD completely lost their ability to sniff around after exposed to two different kinds of odors and showed reduced expression of both growth-associated protein-43-positive immature olfactory sensory neurons (OSNs) and olfactory marker protein-positive mature OSNs in the olfactory epithelium. Since elevated levels of IL-4, IL-13, and IL-6 in the peripheral blood were detected in NC/Tnd mice with AD, injection of neutralizing mAb against IL-4Rα or IL-6 improved olfactory function and expression of OSNs. Furthermore, administration with signal inhibitors targeting IL-4Rα and IL-6Rβ resulted in the recovery of olfactory function. The present findings suggest that the activation of the IL-4Rα and IL-6Rβ signal pathways by AD suppresses the expression of OSNs in the olfactory epithelium, leading to the loss of smell.