Monocyte Heterogeneity and Distinct Monocyte Subsets in Kawasaki Disease Revealed by scRNA-seq

Kawasaki disease (KD) is characterized by a disorder of immune response, and its etiology remains unknown. Monocyte is an important member of body's innate immune system, however its role in KD is still elusive due to its ambiguous heterogeneity and complex functions. Here, scRNA-seq was performed to reveal monocytes heterogeneity in healthy and KD infants. Circulating monocytes were separated from peripheral blood and scRNA-seq was used to transcriptionally profile the monocytes in both healthy and KD infants. Four monocyte subsets are identified in infants, in which three clusters are mainly CD14+CD16- monocytes and one cluster is mainly CD14-CD16+ monocytes. The four monocyte subsets possess different biological functions and represent a relatively linear differentiation. CD14+ monocyte subsets in KD are distinct from that of healthy infants, including one subset expressing FOLR3, S100A12 and IL1R2 and the other expressing MT-TN specifically. Moreover, the CD14+ monocyte subsets in KD are poorly differentiated, and their functions mainly involve neutrophil activation. In conclusion, a relatively comprehensive map of circulating monocyte subsets was plotted for the first time in healthy infants. CD14+ monocyte subsets that are distinct from healthy infants were revealed in KD, which may serve as a target for KD treatment in the future. Overall design: scRNA-Seq of enriched monocytes in 2 healthy infants and 2 KD infants

川崎病（Kawasaki disease, KD）是一类以免疫反应紊乱为特征的疾病，其具体病因至今尚未明确。单核细胞作为机体先天免疫系统的重要组成成员，却因自身异质性模糊、功能复杂，其在川崎病发病过程中的作用仍未得到充分阐释。本研究借助单细胞RNA测序（single-cell RNA sequencing, scRNA-seq），对健康婴儿与川崎病患儿的单核细胞异质性展开解析。研究人员从外周血中分离循环单核细胞，利用scRNA-seq对两组样本的单核细胞进行转录组特征分析。最终共鉴定出4种单核细胞亚群：其中3个聚类主要为CD14+CD16-单核细胞，剩余1个聚类主要为CD14-CD16+单核细胞。这4种单核细胞亚群具备各异的生物学功能，且呈现出相对线性的分化轨迹。川崎病患儿体内的CD14+单核细胞亚群与健康婴儿存在显著差异：一类亚群特异性高表达FOLR3、S100A12及IL1R2，另一类亚群则特异性表达MT-TN。此外，川崎病患儿的CD14+单核细胞亚群分化程度较低，其核心功能主要涉及中性粒细胞活化过程。综上，本研究首次为健康婴儿绘制了较为全面的循环单核细胞亚群图谱；同时揭示了川崎病患儿体内与健康婴儿存在显著差异的CD14+单核细胞亚群，该类亚群未来或可作为川崎病治疗的潜在靶点。研究整体设计：对2名健康婴儿及2名川崎病患儿的富集单核细胞开展scRNA-seq测序。