An essential role for dendritic cells in human and experimental allergic rhinitis

Background: In allergic rhinitis (AR) CD4(+) T(H)2 lymphocytes control inflammation by secreting T(H)2 cytokines, but little is known about how these cells are activated to cause disease. Objective: We sought to study the contribution of antigen-presenting dendritic cells (DCs) in activating TH2 cells and controlling allergic inflammation. Methods: Nasal mucosal biopsy specimens were taken from patients with house dust mite allergy and perennial AR and healthy control subjects. DC numbers were evaluated by using immunohistochemistry. The functional role of DCs was studied in a novel mouse model for AR using BALB/c mice and CD11c-diphtheria toxin (DT) receptor transgenic mice. Results: In symptomatic patients with perennial AR, the number of CD1a(+) and CD11c(+) MHCII+ PCs was higher in the epithelium and lamina propria of the nasal mucosa compared with that seen in healthy control subjects. In patients with AR, DCs had a more mature (CD86(+)) phenotype and were found in close approximation with T lymphocytes. Similarly, in a mouse model of ovalbumin (OVA)-induced AR, CD11c(+) DCs accumulated in areas of nasal eosinophilic inflammation and clustered with CD4(+) T lymphocytes. CD11c(+) DCs were conditionally depleted during allergen challenge by means of systemic administration of DT to CD11c-diphtheria toxin receptor transgenic mice to address the functional role of DCs in maintaining inflammation. In the absence of CD11c(+) DCs, nasal OVA challenge in OVA-sensitized mice did not induce nasal eosinophilia and did not boost OVA-specific IgE levels or T(H)2 cytokine production in the cervical lymph nodes. Conversely, when OVA-pulsed PCs were administered intranasally to sensitized mice, they strongly enhanced OVA-induced nasal eosinophilia and T(H)2 cytokine production. Conclusions: These data in human subjects and mice suggest an essential role for nasal PCs in activation of effector T(H)2 function leading to AR. Clinical implications: Nasal PCs play an essential role in AR and therefore constitute a novel target for therapeutic intervention. Clinical implications: Nasal DCs play an essential role in AR and therefore constitute a novel target for therapeutic intervention.