Immunological landscape of radiation‐induced cardiac injury

Radiation‐induced heart disease (RIHD) is a serious complication of radiotherapy and a major contributor to non‐cancer mortality. This study employs single‐cell RNA sequencing technology to investigate the dynamic immune landscape following radiation‐induced cardiac injury, uncovering potential mechanisms of RIHD and providing strategies for its prevention and treatment. We identified nine immune cell types, totaling 24,683 leukocytes. Macrophages accounted for the largest proportion (78.45%). Over time following irradiation, the proportion of macrophages decreased, while monocytes, T cells, and dendritic cells (DCs) increased. B cells and natural killer cells showed a slight decrease on day 7 but peaked on day 35. Neutrophils reached their highest levels on day 7. We observed a significant increase in pro‐inflammatory subpopulations on day 7 post‐irradiation, along with elevated expression of pro‐inflammatory genes. By day 35, the proportions of apoptosis‐ and proliferation‐related subpopulations had significantly risen, with corresponding upregulation of apoptosis‐ and proliferation‐related genes. We also observed two specific subpopulations: IFN+ macrophages and mregDCs. We identified a fibrosis‐associated macrophage subpopulation, MHCII+_Ccr2 macrophages, and found that the SPP1 pathway was significantly expressed in this subpopulation 7 days post‐irradiation. We further hypothesize that the SPP1‐CD44 pathway may be closely associated with cardiac fibrosis. Thus, this study provides a comprehensive immune atlas of the mouse heart post‐irradiation, revealing significant shifts in immune responses at different time points.