Invariant natural killer T cells in children with eosinophilic esophagitis.

Invariant natural killer T cells in children with eosinophilic esophagitis.
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DOI:
10.1111/cea.12201
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发表时间:
2014-01
期刊:
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
影响因子:
--
通讯作者:
Cianferoni A
Cianferoni A
中科院分区:
其他
文献类型:
--
作者:
Jyonouchi S;Smith CL;Saretta F;Abraham V;Ruymann KR;Modayur-Chandramouleeswaran P;Wang ML;Spergel JM;Cianferoni A

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嗜酸性食管炎(EoE)是一种特应性疾病,其特征是嗜酸性炎症,其中饮食抗原(特别是牛奶)起主要作用。EoE很可能是IgE和非IgE食物介导的混合反应,其中Th 2细胞因子,特别是IL-13的过度表达起主要作用;然而,负责IL-13过度表达的细胞仍然难以捉摸。不变的自然杀伤T细胞受体与鞘脂(SL)连接后,分泌Th 2细胞因子。鞘脂(SL)通过INKT细胞表面的CD 1d分子呈递。牛奶来源的SL已显示激活来自患有IgE介导的对牛奶的食物过敏(FA-MA)的儿童的iNKT以产生Th 2细胞因子。iNKT和牛奶-SL在EoE发病机制中的作用目前尚不清楚。研究iNKT和牛奶-SL在EoE中的作用。对10例活动性EoE(EoE-A)、10例控制性EoE(EoE-C)和16例健康对照(Non-EoE)的外周血单个核细胞(PBMC)进行体外检测,然后与α-半乳糖神经酰胺(αGal)和牛奶-SL孵育。研究了来自外周血(PB)和食管活检的INKT。与EoE-C和非EoE儿童的iNKT相比,EoE-A儿童的外周血iNKT显著更少,对αGal和牛奶-SM的Th 2反应更大。此外,与EoE-C儿童相比,EoE-A儿童食管活检中的iNKT水平升高。Milk-SL能够激活EoE-A儿童的外周血iNKT以产生Th 2细胞因子。此外,在活动性食管嗜酸性粒细胞炎症部位,iNKT水平较高。这项研究表明,牛奶中含有的鞘脂(SL)可能通过促进iNKT细胞介导的Th 2型细胞因子反应,促进嗜酸性粒细胞介导的过敏性炎症,从而推动EoE的发展。
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 over-expression of Th2 cytokines, particularly IL-13, play a major role; however, the cells responsible for IL-13 over-expression remain elusive. Th2-cytokines are secreted following the ligation of invariant natural killer T cell receptors to sphingolipids (SL). Sphingolipids (SL) are presented via the CD1d molecule on the INKT cell 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. 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 esophageal biopsies were studied. EoE-A-children had significantly fewer peripheral blood iNKTs with a greater Th2-response to αGal and milk-SM compared to iNKTs of EoE-C and Non-EoE children. Additionally, EoE-A children had increased iNKT levels in esophageal biopsies compared to 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 esophageal eosinophilic inflammation. This study suggests that sphingolipids (SL) 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.
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