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 T(H)2 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(+) DCs 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 DCs 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 DCs in activation of effector T(H)2 function leading to AR.


CONCLUSIONS
Nasal DCs play an essential role in AR and therefore constitute a novel target for therapeutic intervention.
KleinJan
Alex
A
Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
Willart
Monique
M
van Rijt
Leonie S
LS
Braunstahl
Gert-Jan
GJ
Leman
Karolina
K
Jung
Steffen
S
Hoogsteden
Henk C
HC
Lambrecht
Bart N
BN
D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D039981:Pyroglyphidae / Q000276:immunology; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology* / Q000473:pathology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology