AUTHOR=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 TITLE=Pro-Inflammatory Derangement of the Immuno-Interactome in Heart Failure JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.817514 DOI=10.3389/fimmu.2022.817514 ISSN=1664-3224 ABSTRACT=

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.