Altered miR‐193a‐5p expression in children with cow's milk allergy

发病机制 下调和上调 过敏 外周血单个核细胞 FOXP3型 表观遗传学 小RNA 牛奶过敏 免疫学 DNA甲基化 医学 食物过敏 生物 基因表达 基因 遗传学 免疫系统 体外
作者
Valeria D’Argenio,Valentina Del Monaco,Lorella Paparo,Fatima Domenica Elisa De Palma,Rita Nocerino,Francesca D’Alessio,Feliciano Visconte,Valentina Discepolo,Luigi Del Vecchio,Francesco Salvatore,Roberto Berni Canani
出处
期刊:Allergy [Wiley]
卷期号:73 (2): 379-386 被引量:28
标识
DOI:10.1111/all.13299
摘要

Cow's milk allergy (CMA) is one of the most common food allergies in children. Epigenetic mechanisms have been suggested to play a role in CMA pathogenesis. We have shown that DNA methylation of Th1/Th2 cytokine genes and FoxP3 affects CMA disease course. Preliminary evidence suggests that also the miRNome could be implicated in the pathogenesis of allergy. Main study outcome was to comparatively evaluate miRNome in children with CMA and in healthy controls.Peripheral blood mononuclear cells were obtained from children aged 4-18 months: 10 CMA patients, 9 CMA patients who outgrew CMA, and 11 healthy controls. Small RNA libraries were sequenced using a next-generation sequencing-based approach. Functional assessment of IL-4 expression was also performed.Among the miRNAs differently expressed, 2 were upregulated and 14 were downregulated in children with active CMA compared to healthy controls. miR-193a-5p resulted the most downregulated miRNA in children with active CMA compared to healthy controls. The predicted targets of miR-193a-5p resulted upregulated in CMA patients compared to healthy controls. Peripheral blood CD4+ T cells transfected with a miR193a-5 inhibitor showed a significant upregulation of IL-4 mRNA and its protein expression. Children who outgrew CMA showed miRNA-193a-5p level, and its related targets expression, similar to that observed in healthy controls.Our results suggest that miR-193a-5p is a post-transcriptional regulator of IL-4 expression and could have a role in IgE-mediated CMA. This miRNA could be a novel diagnostic and therapeutic target for this common form of food allergy in childhood.
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