4.1 Article

Single-cell transcriptomics reveal a hyperacute cytokine and immune checkpoint axis after cardiac arrest in patients with poor neurological outcome

Journal

MED
Volume 4, Issue 7, Pages 432-+

Publisher

CELL PRESS
DOI: 10.1016/j.medj.2023.05.003

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Most patients die from neurological injury after cardiac arrest (CA). The systemic inflammatory response after CA is associated with poor outcomes but is not well understood. This study examines the immune cell network induced by CA and identifies specific cell subpopulations and interactions that are associated with poor neurological outcomes.
Background:Most patients hospitalized after cardiac arrest (CA) die because of neurological injury. The systemic inflammatory response after CA is associated with neurological injury and mortality but remains poorly defined. Methods:We determine the innate immune network induced by clinical CA at single-cell resolution. Findings:Immune cell states diverge as early as 6 h post-CA between patients with good or poor neurological outcomes 30 days after CA. Nectin-2+ monocyte and Tim-3+ natural killer (NK) cell subpopulations are associated with poor outcomes, and interactome analysis highlights their crosstalk via cytokines and immune checkpoints. Ex vivo studies of peripheral blood cells from CA patients demonstrate that immune checkpoints are a compensatory mechanism against inflammation after CA. Interferon g (IFNg)/interleukin-10 (IL-10) induced Nectin-2 on monocytes; in a negative feedback loop, Nectin-2 suppresses IFNg production by NK cells. Conclusions:The initial hours after CA may represent a window for therapeutic intervention in the resolution of inflammation via immune checkpoints. Funding:This work was supported by funding from the American Heart Association, Brigham and Women's Hospital Department of Medicine, the Evergreen Innovation Fund, and the National Institutes of Health.

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