Invariant natural killer T cells in children with eosinophilic esophagitis. Issue 1 (January 2014)

• Record Type: Journal Article
• Authors: Jyonouchi, S.; Smith, C. L.; Saretta, F.; Abraham, V.; Ruymann, K. R.; Modayur‐Chandramouleeswaran, P.; Wang, M. ‐L.; Spergel, J. M.; Cianferoni, A.
• Is Part Of: Clinical & experimental allergy. Volume 44:Issue 1(2014:Jan.)
• Page Start: 58
• Page End: 68
• Publication Date: 2014-01
• Subjects: Allergy -- Periodicals; Immunology -- Periodicals; 616.97
• DOI: 10.1111/cea.12201
• Languages: English
• ISSNs: 0954-7894

Abstract

<abstract abstract-type="main" id="cea12201-abs-0001"> <title>Summary</title> <sec id="cea12201-sec-0001" sec-type="section"> <title>Background</title> <p>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.</p> </sec> <sec id="cea12201-sec-0002" sec-type="section"> <title>Objective</title> <p>The aim of this study was to investigate the role of iNKTs and milk‐SL in EoE.</p> </sec> <sec id="cea12201-sec-0003" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="cea12201-sec-0004" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="cea12201-sec-0005" sec-type="section"> <title>Conclusion</title> <p>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.</p> </sec> <sec id="cea12201-sec-0006" sec-type="section"> <title>Clinical Relevance</title> <p>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.</p> </sec> </abstract>