Abstract
Recently, the concept of local allergic rhinitis (LAR) was established, namely rhinitis symptoms with local IgE production and negative serum antigen-specific IgE. However, the natural course of LAR development and the disease pathogenesis is poorly understood. This study investigated the pathophysiology of mice with allergic rhinitis that initially sensitized with ragweed pollen through the nasal route. Mice were nasally administrated ragweed pollen over consecutive days without prior systemic immunization of the allergen. Serial nasal sensitization of ragweed pollen induced an allergen-specific increase in sneezing, eosinophilic infiltration, and the production of local IgE by day 7, but serum antigen-specific IgE was not detected. Th2 cells accumulated in nose and cervical lymph nodes as early as day 3. These symptoms are characteristic of human LAR. Continual nasal exposure of ragweed pollen for 3 weeks resulted in the onset of classical AR with systemic atopy and adversely affected lung inflammation when the allergen was instilled into the lung. Fcer1a −/− mice were defective in sneezing but developed normal eosinophilic infiltration. Contrary, Rag2 −/− mice were defective in both sneezing and eosinophilic infiltration, suggesting that T cells play a central role in the pathogenesis of the disease. These observations demonstrate nasal allergen sensitization to non-atopic individuals can induce LAR. Because local Th2 cell accumulation is the first sign and Th2 cells have a central role in the disease, a T-cell-based approach may aid the diagnosis and treatment of LAR.
Highlights
Allergic rhinitis (AR) is an important health problem because of its prevalence, impact on patient quality of life, and association with asthma
Nasal sensitization of mice with ragweed mimics the symptoms of human local allergic rhinitis (LAR)
To investigate the pathophysiology of patients who were initially sensitized with allergen through the nasal route, we established a novel murine model of AR without systemic immunization (Figure 1A; and Materials and Methods)
Summary
Allergic rhinitis (AR) is an important health problem because of its prevalence, impact on patient quality of life, and association with asthma. AR is induced by nasal allergen exposure that results in IgEmediated inflammation of membranes lining the nose [2]. The allergic response in AR is divided into two phases: early and late [3,4,5]. Allergen-specific IgE is bound to FceRI on the membrane of mast cells and basophils [3]. When they are crosslinked by cognate allergen, mast cells immediately secrete a preformed mediator, histamine, which induces earlyphase responses: sneezing, itching and watery nasal discharge [3,4,5]. Inflammatory cell, e.g. eosinopihls, infiltration into nose mediates the major pathogenic change in the late-phase response. Eosinophils-derived mediators induce epithelial damage resulting in nasal mucosal swelling [3,4,5]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have