Invariant natural killer T cells in children with eosinophilic esophagitis
Article first published online: 20 DEC 2013
© 2013 John Wiley & Sons Ltd
Clinical & Experimental Allergy
Volume 44, Issue 1, pages 58–68, January 2014
How to Cite
Clinical & Experimental Allergy, 2014 (44) 58–68., , , , , , , and ,
- Issue published online: 20 DEC 2013
- Article first published online: 20 DEC 2013
- Accepted manuscript online: 30 SEP 2013 09:34AM EST
- Manuscript Accepted: 6 AUG 2013
- Manuscript Revised: 5 AUG 2013
- Manuscript Received: 23 JAN 2013
- NIH. Grant Numbers: K12HD043245-06, K08 K08 AI089982-01A1
- National Center for Research Resources. Grant Number: UL1-RR-024134
- Eosinophilic esophagitis;
- invariant natural killer T cells;
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.
The aim of this study was to investigate the role of iNKTs and milk-SL in EoE.
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.
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.
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.
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.