Mass cytometry reveals immunological response to radiation-induced cardiac fibrosis in mice

Background Radiation-induced cardiac injury results in complex clinical presentations, unique management issues, and increased morbidity and mortality. But the underlying mechanism of radiation-induced cardiac injury is still unclear. The aim of this study is to explain the compositional alterations of innate and adaptive cells after thoracic irradiation and the relationship of macrophage with other adaptive cells. Methods C57BL/6 mice were anesthetized and performed with 20Gy single dose cardiac irradiation. We carried out mice echocardiography to examine cardiac function. Masson and immunohistochemical staining were adopted to analyze cardiac fibrosis. Blood and cardiac tissue were collected 7 days, 4 weeks and 8 weeks after irradiation and sham-irradiated mice were set as a control group. Part of blood and tissue samples were analyzed with mass cytometry. We also used remaining blood samples to measure pro-fibrotic cytokines. Results We observed reduced cardiac diastolic function and pathologically confirmed cardiac fibrosis after thoracic irradiation. Through mass cytometry, we identified that the proportion of neutrophils, macrophages and monocytes elevated. The ratio of T and B cells decreased after irradiation in the blood samples. For tissue samples, the proportion of macrophages, monocytes and neutrophils increased, endothelial cells reduced, but T and B cells also increased. The level of TGF-β, TNF-α, IL-6 climbed considerably, all of them are closely associated with the evolution of macrophage function during recovering phase of cardiac injury. In the correlation plot, we also discovered that CD4+T and CD8+T cells were strongly positively correlated with macrophages. Conclusion We illustrated the immunological response after radiation-induced cardiac fibrosis, and macrophage may play a crucial role during the process. The results might have therapeutic potential for targeting macrophages in order to reduce radiation-induced cardiac fibrosis. ### Competing Interest Statement The authors have declared no competing interest.