1. Invariant natural killer T cells in children with eosinophilic esophagitis.
- Author
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Jyonouchi S, Smith CL, Saretta F, Abraham V, Ruymann KR, Modayur-Chandramouleeswaran P, Wang ML, Spergel JM, and Cianferoni A
- Subjects
- Adolescent, Allergens immunology, Animals, Child, Child, Preschool, Cytokines biosynthesis, Eosinophilic Esophagitis drug therapy, Eosinophilic Esophagitis metabolism, Female, Humans, Immunophenotyping, Lymphocyte Count, Male, Milk immunology, Natural Killer T-Cells metabolism, Phenotype, Receptors, CCR3 metabolism, Receptors, CCR4 metabolism, Receptors, CCR5 metabolism, Th2 Cells immunology, Th2 Cells metabolism, Eosinophilic Esophagitis immunology, Natural Killer T-Cells immunology
- Abstract
Background: Eosinophilic esophagitis (EoE) is an atopic disease characterized by eosinophilic inflammation in which dietary antigens (in particular, milk) play a major role. EoE is most likely a mixed IgE and non-IgE food-mediated reaction in which overexpression of Th2 cytokines, particularly IL-13, play a major role; however, the cells responsible for IL-13 overexpression remain elusive. Th2-cytokines are secreted following the ligation of invariant natural killer T cell receptors to sphingolipids (SLs). Sphingolipids (SLs) are presented via the CD1d molecule on the INKTs surface. Cow's milk-derived SL has been shown to activate iNKTs from children with IgE-mediated food allergies to milk (FA-MA) to produce Th2 cytokines. The role of iNKTs and milk-SL in EoE pathogenesis is currently unknown., Objective: The aim of this study was to investigate the role of iNKTs and milk-SL in EoE., Methods: Peripheral blood mononuclear cells (PBMCs) from 10 children with active EoE (EoE-A), 10 children with controlled EoE (EoE-C) and 16 healthy controls (non-EoE) were measured ex vivo and then incubated with α-galactosylceramide (αGal) and milk-SL. INKTs from peripheral blood (PB) and oesophageal biopsies were studied., Results: EoE-A children had significantly fewer peripheral blood iNKTs with a greater Th2-response to αGal and milk-SM compared with iNKTs of EoE-C and non-EoE children. Additionally, EoE-A children had increased iNKT levels in oesophageal biopsies compared with EoE-C children., Conclusion: Milk-SLs are able to activate peripheral blood iNKTs in EoE-A children to produce Th2 cytokines. Additionally, iNKT levels are higher at the site of active oesophageal eosinophilic inflammation., Clinical Relevance: This study suggests that sphingolipids (SLs) contained in milk may drive the development of EoE by promoting an iNKT-cell-mediated Th2-type cytokine response that facilitates eosinophil-mediated allergic inflammation., (© 2013 John Wiley & Sons Ltd.)
- Published
- 2014
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