Ruiz Vanessa Y, Calderon Tina M, Leon-Rivera Rosiris, Chilunda Vanessa, Zhang Jinghang, Berman Joan W
Department of Pathology, Albert Einstein College of Medicine, New York, NY, United States.
Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, United States.
Front Immunol. 2025 Feb 20;16:1475480. doi: 10.3389/fimmu.2025.1475480. eCollection 2025.
Monocytes in the central nervous system (CNS) play a pivotal role in surveillance and homeostasis, and can exacerbate pathogenic processes during injury, infection, or inflammation. CD14CD16 monocytes exhibit diverse functions and contribute to neuroinflammatory diseases, including HIV-associated neurocognitive impairment (HIV-NCI). Analysis of human CD14CD16 monocytes matured by single-cell RNA sequencing identified a heterogenous population of nine clusters. Ingenuity pathway analysis of differentially expressed genes in each cluster identified increased migratory and inflammatory pathways for a group of clusters, which we termed Group 1 monocytes. Group 1 monocytes, distinguished by increased ALCAM, CD52, CD63, and SDC2, exhibited gene expression signatures implicated in CNS inflammatory diseases, produced higher levels of CXCL12, IL-1Ra, IL-6, IL-10, TNFα, and ROS, and preferentially transmigrated across a human blood-brain barrier model. Thus, Group 1 cells within the CD14CD16 monocyte subset are likely to be major contributors to neuroinflammatory diseases.
中枢神经系统（CNS）中的单核细胞在监测和体内平衡中起关键作用，并且在损伤、感染或炎症期间会加剧致病过程。CD14CD16单核细胞具有多种功能，并与神经炎症性疾病有关，包括与HIV相关的神经认知障碍（HIV-NCI）。通过单细胞RNA测序对成熟的人类CD14CD16单核细胞进行分析，确定了一个由九个簇组成的异质群体。对每个簇中差异表达基因的 Ingenuity 通路分析确定了一组簇的迁移和炎症通路增加，我们将其称为第1组单核细胞。第1组单核细胞以ALCAM、CD52、CD63和SDC2的增加为特征，表现出与中枢神经系统炎症性疾病相关的基因表达特征，产生更高水平的CXCL12、IL-1Ra、IL-6、IL-10、TNFα和ROS，并优先穿过人血脑屏障模型迁移。因此，CD14CD16单核细胞亚群中的第1组细胞可能是神经炎症性疾病的主要促成因素。
