Significance of para-esophageal lymph nodes in food or aeroallergen-induced iNKT cell-mediated experimental eosinophilic esophagitis

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2012-04, Vol.302 (7), p.G645-G654
• Main Authors: Rajavelu, Priya, Rayapudi, Madhavi, Moffitt, Matthew, Mishra, Akanksha, Mishra, Anil
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD1d - genetics; Antigens, CD1d - immunology; Arachis - immunology; Aspergillus; Call for Papers; Cells; Chemokine CCL11 - genetics; Chemokine CCL11 - immunology; Chemokine CCL24 - genetics; Chemokine CCL24 - immunology; Cytokines; Eosinophilic Esophagitis - etiology; Eosinophilic Esophagitis - immunology; Eosinophilic Esophagitis - pathology; Esophagus - immunology; Esophagus - pathology; Female; Food allergies; Food Hypersensitivity - complications; Food Hypersensitivity - immunology; Immunoglobulin E - metabolism; Inflammatory diseases; Inhalation Exposure; Lymph Nodes - immunology; Lymph Nodes - physiology; Male; Mast Cells - cytology; Mice; Mice, Inbred BALB C; Natural Killer T-Cells - physiology; Plant Extracts - administration & dosage; Plant Extracts - immunology; Rodents; Specific Pathogen-Free Organisms; Zea mays - immunology
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.00223.2011

Eosinophilic esophagitis (EoE) is a recently recognized inflammatory disorder driven by food hypersensitivity; however, the specific foods and mechanisms involved are unclear. In patients with EoE, we have found that hypersensitivities to corn and peanuts are the most common. Accordingly, we sensitized and exposed mice either intranasally or intragastrically with corn or peanut extract or saline. Esophageal eosinophilia, the genes of eosinophil-directed cytokines, and allergen-induced antibodies were examined in mice challenged with corn or peanut extract or saline. A high number of esophageal lamina propria eosinophils as well as eosinophilic microabscesses, intraepithelial eosinophils, extracellular eosinophilic granules, thickened and disrupted epithelial mucosa, and mast cell hyperplasia were observed in the esophagus of peanut or corn allergen-challenged mice. Mechanistic analysis indicated that para-esophageal lymph nodes might be critical in the trafficking of eosinophils to the esophagus and in EoE association to airway eosinophilia. Furthermore, experimentation with gene-targeted mice revealed that peanut allergen-induced EoE was dependent on eotaxin and invariant natural killer T (iNKT) cells, as CD1d and eotaxin-1/2 gene-deficient mice were protected from disease induction. Thus we provide evidence that para-esophageal lymph nodes are involved in food- or aeroallergen-induced eosinophilia and patchy EoE pathogenesis, likely a mechanism dependent on eotaxins and iNKT cells.