Invariant natural killer T cells in children with eosinophilic esophagitis

Summary 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, particularl...

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Bibliographic Details
Published in:Clinical and experimental allergy 2014-01, Vol.44 (1), p.58-68
Main Authors: Jyonouchi, S., Smith, C. L., Saretta, F., Abraham, V., Ruymann, K. R., Modayur-Chandramouleeswaran, P., Wang, M. -L., Spergel, J. M., Cianferoni, A.
Format: Article
Language:English
Subjects:
Adolescent
Allergens - immunology
Animals
Biopsy
Child
Child, Preschool
Cytokines
Cytokines - biosynthesis
Eosinophilic esophagitis
Eosinophilic Esophagitis - drug therapy
Eosinophilic Esophagitis - immunology
Eosinophilic Esophagitis - metabolism
Female
Humans
Immune system
Immunophenotyping
invariant natural killer T cells
Lymphocyte Count
Male
Milk
Milk - immunology
Natural Killer T-Cells - immunology
Natural Killer T-Cells - metabolism
Phenotype
Receptors, CCR3 - metabolism
Receptors, CCR4 - metabolism
Receptors, CCR5 - metabolism
sphingolipids
T cell receptors
Th2 Cells - immunology
Th2 Cells - metabolism
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Summary:Summary 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.
ISSN:0954-7894
1365-2222
DOI:10.1111/cea.12201