心臓マクロファージサブセットと機能の加齢に伴う変容

抄録

The prevalence of heart failure is increasing in the aging society. We previously demonstrated that cardiac Ly6C^lo macrophages play key roles in the maintenance of homeostasis and stress response in the heart. Because cardiac macrophages are crucial for cardiac homeostasis, we hypothesized that age-associated alterations of cardiac macrophages might impair cardiac homeostasis in the elderly. To better understand the age-associated changes in cardiac macrophages, we performed single-cell RNA-sequencing (scRNA-seq). Our scRNA-seq data demonstrated that cardiac macrophages consisted of multiple subsets. We found that the several tissue-resident macrophage subsets that appear to contribute to homeostasis were replaced with aged mice-specific subsets. Interestingly, aging is associated with increased levels of circulating proinflammatory cytokines and chemokines, whereas, our scRNA-seq data revealed lower expression levels of Ccl4 in aged mice-specific cardiac macrophages. These results suggest that alteration of the expression of chemokines in cardiac macrophages may result in changes in the proportion of each immune cell population in the heart of aged mice, triggering age-associated disease induction. In this symposium, we will discuss the physiological and pathological consequences of altered chemokine expression in cardiac macrophages.