Table_1_Epigenetic Differences in Long Non-coding RNA Expression in Finnish and Russian Karelia Teenagers With Contrasting Risk of Allergy and Asthma.XLSX

BackgroundPreviously, we investigated skin microbiota and blood cell gene expression in Finnish and Russian teenagers with contrasting incidence of allergic conditions. The microbiota and transcriptomic signatures were distinctly different, with high Acinetobacter abundance and suppression of genes regulating innate immune response in healthy subjects.
ObjectiveHere, we investigated long non-coding RNA (lncRNA) expression profiles of blood mononuclear cells (PBMC) from healthy and allergic subjects, to identify lncRNAs that act at the interphase of microbiome-mediated immune homeostasis in allergy/asthma.
MethodsGenome-wide co-expression network analyses of blood cell lncRNA/mRNA expression was integrated with skin microbiota profiles of Finnish (69) and Russian (75) subjects. Selected lncRNAs were validated by stimulation of cohort-derived PBMCs and a macrophage cell model with birch pollen allergen (Betv1) or lipopolysaccharide, respectively.
ResultsFinnish and Russian PBMCs were differentiated by 3,818 lncRNA transcripts. In the Finnish subjects with high prevalence of allergy and asthma, a subset of 37 downregulated lncRNAs (including, FAM155A-IT1 and LOC400958) were identified. They were part of a co-expression network with 20 genes known to be related to asthma and allergic rhinitis (R > 0.95). Incidentally, all these 20 genes were also components of pathways corresponding to cellular response to bacterium. The Finnish and Russian samples were also differentiated by the abundance of 176 bacterial OTU (operational taxonomic units). The subset of 37 lncRNAs, associated with allergy, was most correlated with the abundance of Acinetobacter (R > +0.5), Jeotgalicoccus (R > +0.5), Corynebacterium (R < −0.5) and Micrococcus (R < −0.5).
ConclusionIn Finnish and Russian teenagers with contrasting allergy and asthma prevalence, epigenetic differences in lncRNA expression appear to be important components of the underlying microbiota-immune interactions. Unraveling the functions of the 37 differing lncRNAs may be the key to understanding microbiome-immune crosstalk, and to develop clinically relevant biomarkers.

研究背景：此前，我们针对过敏发病情况迥异的芬兰与俄罗斯青少年群体，开展了皮肤微生物组与血细胞基因表达的相关研究。研究发现，两组人群的微生物组与转录组特征存在显著差异：健康受试者体内不动杆菌属（Acinetobacter）丰度较高，同时其调控固有免疫应答的基因表达受到抑制。
研究目的：本研究聚焦健康与过敏受试者的外周血单个核细胞（peripheral blood mononuclear cell, PBMC）长链非编码RNA（long non-coding RNA, lncRNA）表达谱，旨在筛选在过敏/哮喘中参与微生物组介导的免疫稳态界面调控的lncRNA。
研究方法：我们将血细胞lncRNA/信使RNA（messenger RNA, mRNA）的全基因组共表达网络分析结果，与芬兰（69例）、俄罗斯（75例）受试者的皮肤微生物组特征进行整合分析。通过分别用桦树花粉过敏原（Betv1）与脂多糖刺激该研究队列来源的PBMC及巨噬细胞模型，对筛选得到的目标lncRNA进行验证。
研究结果：芬兰与俄罗斯受试者的PBMC可通过3818个lncRNA转录本进行有效区分。在过敏与哮喘患病率较高的芬兰受试者群体中，我们筛选得到37个表达下调的lncRNA（包括FAM155A-IT1与LOC400958）。这些lncRNA隶属于一个共表达网络，该网络包含20个已知与哮喘、过敏性鼻炎相关的基因（相关系数R>0.95）。值得注意的是，这20个基因均属于细菌细胞应答相关通路。此外，芬兰与俄罗斯样本还可通过176个细菌操作分类单元（operational taxonomic units, OTU）的丰度特征进行区分。与过敏相关的37个lncRNA亚组，与不动杆菌属（Acinetobacter）（R>+0.5）、杰氏球菌属（Jeotgalicoccus）（R>+0.5）的丰度呈显著正相关，与棒状杆菌属（Corynebacterium）（R<−0.5）、微球菌属（Micrococcus）（R<−0.5）的丰度呈显著负相关。
研究结论：在过敏与哮喘患病率迥异的芬兰与俄罗斯青少年群体中，lncRNA表达的表观遗传差异似乎是微生物组-免疫互作调控机制的重要组成部分。解析这37个差异表达lncRNA的功能，或可为理解微生物组-免疫串扰机制、开发临床相关生物标志物提供关键突破口。