Olfactory dysfunction associated with atopic dermatitis in NC/Tnd mice

Area of Science:

• Immunology
• Neuroscience
• Dermatology

Background:

• Atopic dermatitis (AD) is a chronic inflammatory skin condition often linked to mental health issues like depression.
• Depression is associated with olfactory dysfunction (anosmia), but the connection between AD and smell loss remains unexplored.
• NC/Tnd mice, a model for spontaneous AD, exhibit depressive symptoms, making them suitable for studying AD-related olfactory changes.

Purpose of the Study:

• To investigate whether atopic dermatitis (AD) causes olfactory dysfunction.
• To explore the underlying mechanisms of AD-induced smell loss in NC/Tnd mice.
• To assess the therapeutic potential of targeting specific inflammatory pathways for olfactory recovery.

Main Methods:

• NC/Tnd mice, an AD model, were used to assess olfactory function after odor exposure.
• Expression levels of immature (GAP-43+) and mature (OMP+) olfactory sensory neurons (OSNs) were evaluated.
• The effects of neutralizing antibodies against IL-4Rα and IL-6, and signal inhibitors for IL-4Rα and IL-6Rβ, on olfactory function and OSN expression were examined.

Main Results:

• AD model mice exhibited complete loss of odor detection ability.
• Reduced expression of both immature and mature olfactory sensory neurons (OSNs) was observed in the olfactory epithelium of AD mice.
• Elevated levels of IL-4, IL-13, and IL-6 were detected in AD mice; targeted inhibition of IL-4Rα and IL-6Rβ signaling pathways restored olfactory function and OSN expression.

Conclusions:

• Atopic dermatitis (AD) leads to olfactory dysfunction, characterized by the loss of smell.
• The inflammatory pathways involving IL-4Rα and IL-6Rβ activation suppress olfactory sensory neuron (OSN) expression in the olfactory epithelium.
• Targeting these specific inflammatory pathways offers a potential therapeutic strategy for restoring olfactory function in AD patients.