Chao Wen-Cheng, Liao Wen-Ting, Wang Jing-Rong, Sung Hsiao-Ni, Chen Hsin-Hua, Lin Fang-Ping, Huang Jou-Yu, Liu Kuan-Ting, Ko Tai-Ming
Department of Critical Care Medicine Taichung Veterans General Hospital Taichung Taiwan.
Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu Taiwan.
Clin Transl Allergy. 2022 May 5;12(5):e12151. doi: 10.1002/clt2.12151. eCollection 2022 May.
Hymenoptera stings can induce dysregulated inflammation and immediate hypersensitivity reactions including anaphylaxis. However, the molecular mechanisms underlying peripheral immune responses during Hymenoptera venom allergy (HVA) remain elusive.
Here we determined the single-cell transcriptomic profiling from highly heterogeneous peripheral blood cells in patients with HVA through unbiased single-cell RNA sequencing and multiple models of computational analyses.
Through clustering analysis by uniform manifold approximation and projection, we revealed an increased number of monocytes in the acute phase and identified innate immune responses, leukocyte activation, and cellular detoxification as the main involved biological processes. We used filter analysis to identify that CLU that encodes clusterin was highly expressed in monocytes, and the co-expressed genes of CLU further supported the key role of monocyte. We further used pseudo-temporal ordering of cells and scRNA velocity analysis to delineate disease-associated monocyte lineages and states in patients with HVA.
Our comprehensive molecular profiling of blood samples from patients with HVA revealed previously unknown molecular changes, providing important insights into the mechanism of venom allergy and potential therapeutic targets.
膜翅目昆虫叮咬可引发炎症失调和包括过敏反应在内的速发型超敏反应。然而，膜翅目昆虫毒液过敏（HVA）期间外周免疫反应的分子机制仍不清楚。
在此，我们通过无偏单细胞RNA测序和多种计算分析模型，确定了HVA患者高度异质外周血细胞的单细胞转录组图谱。
通过均匀流形近似和投影进行聚类分析，我们发现急性期单核细胞数量增加，并确定先天免疫反应、白细胞激活和细胞解毒是主要涉及的生物学过程。我们使用过滤分析确定编码簇集素的CLU在单核细胞中高表达，CLU的共表达基因进一步支持了单核细胞的关键作用。我们进一步使用细胞的伪时间排序和scRNA速度分析来描绘HVA患者中与疾病相关的单核细胞谱系和状态。
我们对HVA患者血样进行的全面分子分析揭示了以前未知的分子变化，为毒液过敏机制和潜在治疗靶点提供了重要见解。
