Kumar Pavanish, Lim Amanda, Poh Su Li, Hazirah Sharifah Nur, Chua Camillus Jian Hui, Sutamam Nursyuhadah Binte, Arkachaisri Thaschawee, Yeo Joo Guan, Kofidis Theo, Sorokin Vitaly, Lam Carolyn S P, Richards Arthur Mark, Albani Salvatore
Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore.
KK Research Centre, KK Women's and Children's Hospital, Singapore, Singapore.
Front Immunol. 2022 Mar 15;13:817514. doi: 10.3389/fimmu.2022.817514. eCollection 2022.
Chronic heart failure (HF) is a syndrome of heterogeneous etiology associated with multiple co-morbidities. Inflammation is increasingly recognized as a key contributor to the pathophysiology of HF. Heterogeneity and lack of data on the immune mechanism(s) contributing to HF may partially underlie the failure of clinical trials targeting inflammatory mediators. We studied the Immunome in HF cohort using mass cytometry and used data-driven systems immunology approach to discover and characterize modulated immune cell subsets from peripheral blood. We showed cytotoxic and inflammatory innate lymphoid and myeloid cells were expanded in HF patients compared to healthy controls. Network analysis showed highly modular and centralized immune cell architecture in healthy control immune cell network. In contrast, the HF immune cell network showed greater inter-cellular communication and less modular structure. Furthermore, we found, as an immune mechanism specific to HF with preserved ejection fraction (HFpEF), an increase in inflammatory MAIT and CD4 T cell subsets.
慢性心力衰竭（HF）是一种病因异质性且伴有多种合并症的综合征。炎症日益被认为是HF病理生理学的关键促成因素。HF免疫机制的异质性和数据缺失可能是针对炎症介质的临床试验失败的部分原因。我们使用质谱流式细胞术研究了HF队列中的免疫组，并采用数据驱动的系统免疫学方法从外周血中发现并表征受调节的免疫细胞亚群。我们发现，与健康对照相比，HF患者中具有细胞毒性和炎症性的先天性淋巴细胞和髓细胞有所增加。网络分析显示，健康对照免疫细胞网络具有高度模块化和集中化的免疫细胞结构。相比之下，HF免疫细胞网络表现出更强的细胞间通讯和更低的模块化结构。此外，我们发现，作为射血分数保留的HF（HFpEF）特有的一种免疫机制，炎症性黏膜相关恒定T细胞（MAIT）和CD4 T细胞亚群有所增加。
