尘螨过敏原免疫治疗对过敏性哮喘患儿树突状细胞表型变化的影响
2013/03/28
摘要
背景:过敏性哮喘是一种Th2炎症性疾病。树突状细胞(DCs)在Th1/Th2平衡中起到关键作用。过敏原特异性免疫治疗(SIT)能提高Th1/Th2细胞因子比例,因而能改变过敏症的病程。
目的:本试验研究SIT对儿童DCs的影响,并确定该治疗方法的新参数。
方法:本试验研究接受完全尘螨SIT的过敏性哮喘患儿的单核细胞来源的DCs的表型变化和功能变异。收集SIT的过敏性哮喘患儿、过敏性哮喘对照者和健康对照者的外周血单核细胞并培养,采用粒细胞-巨噬细胞集落刺激因子和白介素-4刺激,随后采用屋尘螨(Der p)过敏原或脂多糖(LPS)刺激。单核细胞来源的DCs表面分子表达采用流式细胞仪检测。培养的单核细胞来源的DCs,其细胞因子生成量采用酶联免疫法检测。
结果:在经过LPS刺激后,与对照者相比,过敏性哮喘患儿单核细胞来源的DCs CD86表达较高、HLA-DR表达较低。在SIT患者中,上述两个分子表达水平与健康对照者类似。在经过Der p刺激后,过敏性哮喘患儿单核细胞来源的DCs Toll样受体4(TLR4)表达较低。与健康者相比,SIT患者的TLR4表达与健康对照者相似。
结论:这些结果显示,SIT能使DCs的CD86、HLA-DR和TLR4表达恢复正常。此外,CD86、HLA-DR和TLR4可用于监测SIT。过敏性哮喘患者TLR4表达下降可通过TLR激动剂所代偿,可放大SIT的疗效。
(刘国梁 审校)
AnnAllergyAsthmaImmunol.2013Feb;110(2):107-12.doi:10.1016/j.anai.2012.11.09. Epub 2012 Dec 21.
Effect of mite allergen immunotherapy on the altered phenotype of dendritic cells in allergic asthmatic children.
Wang CM, Chuang JJ.
Source
Department of Pediatrics, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan.
Abstract
BACKGROUND: Allergic asthma is a T(H)2 inflammatory disease. Dendritic cells (DCs) play key roles in the T(H)1/T(H)2 balance. Allergen specific immunotherapy (SIT) has the potential to modify the course of allergy because the ratio of T(H)1 to T(H)2 cytokines produced is increased after SIT.
OBJECTIVE: To determine how SIT affects DCs in children and to define novel parameters of this treatment.
METHODS: We investigated the changes of phenotypic and functional variations of monocyte-derived DCs from allergic asthmatic children undergoing complete mite SIT. Peripheral blood monocytes from SIT allergic asthmatic children, allergic asthmatic controls, and healthy controls were cultured with granulocyte-macrophage colony-stimulating factor and interleukin 4 and then stimulated with Dermatophagoides pteronyssinus (Der p) allergen or lipopolysaccharide (LPS). The expressions of surface molecules on monocyte-derived DCs were assessed by flow cytometry. Cytokine production by cultured monocyte-derived DCs was determined by enzyme-linked immunosorbent assay.
RESULTS: After LPS stimulation, monocyte-derived DCs of the allergic asthmatic group had a higher CD86 and lower HLA-DR expression than the healthy controls. In SIT patients, the expression was similar to that of the healthy controls. After Der p stimulation monocyte-derived DCs of the allergic asthmatic patients displayed lower Toll-like receptor 4 (TLR4), whereas again in SIT patients the expression was similar to that of healthy controls.
CONCLUSION: These findings indicate that SIT normalizes the expression of CD86, HLA-DR, and TLR4 on DCs. Moreover, CD86, HLA-DR, and TLR4 may be useful parameters for monitoring SIT. Decreased TLR4 expression in allergic asthmatic patients might be compensated by TLR4 agonists, with the potential of amplifying the effects of SIT.
AnnAllergy Asthma Immunol.2013Feb;110(2):107-12.doi:10.1016/j.anai.2012.11.019. Epub 2012 Dec 21.
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