Shen Jie, He Yunyan, Zheng Hong, Xiao Jianwen, Li Fu, Chen Keke, Guo Biyun, He Yulei, Liu Lin, Lin Zhi, Wang Dan, Liu Leping, Wang Shengfeng, Zhou Wen, Zhang Yingchi, Wei Jian, Wang Yunchu, Hu Rong, Tang Daolin, Wang Dao, Yang Minghua
Department of Pediatrics, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Hunan Clinical Research Center of Pediatric Cancer, Changsha, Hunan, China.
Nat Commun. 2025 Jul 25;16(1):6888. doi: 10.1038/s41467-025-62090-5.
Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a fatal hyperinflammatory disorder distinct from self-limiting EBV-induced infectious mononucleosis (IM). However, the immunological mechanisms underlying the divergence between benign EBV infection and fulminant HLH-particularly in the absence of inherited immunodeficiency-remains unclear, and systematic comparisons of immune landscapes across EBV-associated disease spectra are lacking. In this study, by enrolling children with IM and healthy volunteers as controls, we utilize single-cell RNA sequencing to identify unique immunological characteristics of EBV-HLH. Our analysis indicates that patients with EBV-HLH exhibite widespread activation of NF-κB signaling pathway. Furthermore, excessive cytokine secretion by T and NK cells is observed, along with a shift in monocyte differentiation towards an inflammatory phenotype, and the aggregation of IDO1 monocytes. Metabolic pathway analysis reveals that L-kynurenine, a downstream metabolite of IDO1, is specifically elevated in EBV-HLH and mediates the production of multiple pro-inflammatory cytokines. Collectively, our study maps the immune landscape in pediatric EBV-HLH at single-cell resolution, uncovering potential role of IDO1 monocytes and L-kynurenine as biomarkers.
爱泼斯坦-巴尔病毒相关噬血细胞性淋巴组织细胞增生症（EBV-HLH）是一种致命的高炎症性疾病，与自限性EBV诱导的传染性单核细胞增多症（IM）不同。然而，良性EBV感染与暴发性HLH之间差异的免疫机制，尤其是在没有遗传性免疫缺陷的情况下，仍不清楚，并且缺乏对EBV相关疾病谱的免疫格局的系统比较。在本研究中，我们招募患有IM的儿童和健康志愿者作为对照，利用单细胞RNA测序来确定EBV-HLH独特的免疫特征。我们的分析表明，EBV-HLH患者表现出NF-κB信号通路的广泛激活。此外，观察到T细胞和NK细胞过度分泌细胞因子，同时单核细胞分化向炎症表型转变，以及IDO1单核细胞聚集。代谢途径分析显示，IDO1的下游代谢产物L-犬尿氨酸在EBV-HLH中特异性升高，并介导多种促炎细胞因子的产生。总的来说，我们的研究以单细胞分辨率描绘了儿童EBV-HLH的免疫格局，揭示了IDO1单核细胞和L-犬尿氨酸作为生物标志物的潜在作用。
