Significance of para-esophageal lymph nodes in food or aeroallergen-induced iNKT cell-mediated experimental eosinophilic esophagitis.
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.
Department of Pediatrics, Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Priya
P
Rajavelu
Madhavi
M
Rayapudi
Matthew
M
Moffitt
Akanksha
A
Mishra
Anil
A
Mishra
D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology; D010367:Arachis / Q000276:immunology; D001230:Aspergillus; D054413:Chemokine CCL11 / Q000235:genetics / Q000276:immunology; D054423:Chemokine CCL24 / Q000235:genetics / Q000276:immunology; D057765:Eosinophilic Esophagitis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D004947:Esophagus / Q000276:immunology / Q000473:pathology; D005260:Female; D005512:Food Hypersensitivity / Q000150:complications / Q000276:immunology*; D007073:Immunoglobulin E / Q000378:metabolism; D019570:Inhalation Exposure; D008198:Lymph Nodes / Q000276:immunology / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D055611:Natural Killer T-Cells / Q000502:physiology*; D010936:Plant Extracts / Q000008:administration & dosage / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D003313:Zea mays / Q000276:immunology
D055610:Antigens, CD1d; C515457:Ccl11 protein, mouse; C515485:Ccl24 protein, mouse; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D010936:Plant Extracts; D007073:Immunoglobulin E