Epigenetic programming underpins B-cell dysfunction in peanut and multi-food allergy.
Epigenetic programming underpins B-cell dysfunction in peanut and multi-food allergy.
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DOI：
10.1002/cti2.1324
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发表时间：
2021
影响因子：
5.8
通讯作者：
Saffery R
中科院分区：
文献类型：
--
作者：
Imran S;Neeland MR;Koplin J;Dharmage S;Tang ML;Sawyer S;Dang T;McWilliam V;Peters R;Perrett KP;Novakovic B;Saffery R
在过去的几十年里，IgE 介导的食物过敏 (FA) 的发生率有所增加，越来越多的证据表明 FA 发育过程中各种免疫细胞类型的表观遗传谱受到破坏。最近的数据表明 FA 中 B 细胞功能障碍；然而，很少有研究检查这些细胞内的表观遗传变化。我们评估了 FA 青少年纯化 B 细胞的表观遗传和转录组谱，比较了单一食物过敏（仅花生）、多种食物过敏（花生和 ≥1 种其他食物）和非过敏（对照）个体。青少年表现出持续且严重的 FA 表型，表明存在常见的免疫偏差。我们鉴定了 144 个差异甲基化探针 (DMP) 和 116 个差异表达基因 (DEG)，可将 FA 患者的 B 细胞与对照组区分开来，包括先前与过敏性疾病相关的 PM20D1 启动子的差异甲基化。亚组比较发现 729 个 DMP 对单一食物或多种食物过敏个体具有特异性，这表明过敏组之间存在表观遗传差异。这包括多种食物过敏个体中三个 S100 基因附近甲基化增加的两个区域。多种食物过敏个体特有的 DEG 本体论结果揭示了与骨髓细胞激活相关的术语的丰富。与 DMP 和 DEG 相关的启动子的基序富集分析显示，多种食物过敏组和单一食物过敏组之间调节 B 细胞和 T 细胞发育的转录因子、B 细胞谱系测定和 TGF-β 信号通路所识别的基序存在差异富集。我们的数据强调了与花生过敏相关的 B 细胞的表观遗传变化，区分了单一食物和多种食物过敏个体的表观基因组特征，并揭示了可能支撑这些不同表型的差异发育途径。这项研究评估了一组单一食物过敏、多种食物过敏和非过敏对照组的表观基因组和转录组。我们在食物过敏青少年中发现了独特的 B 细胞表观遗传特征，并进一步发现了多种食物过敏特异性甲基化特征，描绘了这些临床群体中关键免疫途径的差异调节。
Rates of IgE‐mediated food allergy (FA) have increased over the last few decades, and mounting evidence implicates disruption of epigenetic profiles in various immune cell types in FA development. Recent data implicate B‐cell dysfunction in FA; however, few studies have examined epigenetic changes within these cells. We assessed epigenetic and transcriptomic profiles in purified B cells from adolescents with FA, comparing single‐food‐allergic (peanut only), multi‐food‐allergic (peanut and ≥1 other food) and non‐allergic (control) individuals. Adolescents represent a phenotype of persistent and severe FA indicative of a common immune deviation. We identified 144 differentially methylated probes (DMPs) and 116 differentially expressed genes (DEGs) that distinguish B cells of individuals with FA from controls, including differential methylation of the PM20D1 promoter previously associated with allergic disorders. Subgroup comparisons found 729 DMPs specific to either single‐food‐ or multi‐food‐allergic individuals, suggesting epigenetic distinctions between allergy groups. This included two regions with increased methylation near three S100 genes in multi‐food‐allergic individuals. Ontology results of DEGs specific to multi‐food‐allergic individuals revealed enrichment of terms associated with myeloid cell activation. Motif enrichment analysis of promoters associated with DMPs and DEGs showed differential enrichment for motifs recognised by transcription factors regulating B‐ and T‐cell development, B‐cell lineage determination and TGF‐β signalling pathway between the multi‐food‐allergic and single‐food‐allergic groups. Our data highlight epigenetic changes in B cells associated with peanut allergy, distinguishing features of the epigenome between single‐food‐ and multi‐food‐allergic individuals and revealing differential developmental pathways potentially underpinning these distinct phenotypes. This study assessed epigenomes and transcriptomes from a cohort of single‐food‐allergic, multi‐food‐allergic and non‐allergic controls. We found distinct B‐cell epigenetic signatures in food‐allergic adolescents and further uncovered multi‐food allergy‐specific methylation signatures, depicting differential regulation of key immune pathways in these clinical groups.
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影响因子：
14.2
作者：
Bock, SA;Muñoz-Furlong, A;Sampson, HA
通讯作者：
Sampson, HA
影响因子：
4.4
作者：
Alduraywish, Shatha A.;Lodge, Caroline J.;Dharmage, Shyamali C.
通讯作者：
Dharmage, Shyamali C.
影响因子：
32.4
作者：
Elo, Laura L.;Jarvenpaa, Henna;Lahesmaa, Riitta
通讯作者：
Lahesmaa, Riitta
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
过敏原特异性IgG（+）内存B细胞在时间上链接到IgE内存响应。
DOI：
10.1016/j.jaci.2019.11.046
发表时间：
2020-07
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Hoof I;Schulten V;Layhadi JA;Stranzl T;Christensen LH;Herrera de la Mata S;Seumois G;Vijayanand P;Lundegaard C;Niss K;Lund A;Ahrenfeldt J;Holm J;Steveling E;Sharif H;Durham SR;Peters B;Shamji MH;Andersen PS
通讯作者：
Andersen PS