中文摘要：
中风的医疗负担超出了脑损伤本身，很大程度上是由继发性慢性合并症决定的。我们假设这些合并症可能有一个共同的免疫学原因，但中风后对全身免疫的慢性影响尚未得到充分探索。在这里，我们将髓系先天免疫记忆确定为中风后远端器官功能障碍的原因。单细胞测序显示，在脑损伤后长达 3 个月的多个器官（尤其是心脏）中，单核细胞/巨噬细胞持续存在促炎变化，导致小鼠和中风患者的心脏纤维化和功能障碍。IL-1β被确定为先天免疫记忆表观遗传变化的关键驱动因素。这些变化可以移植到幼稚小鼠身上，诱发心功能障碍。通过中和中风后的IL-1β或用CCR2/5抑制剂阻断促炎性单核细胞运输，我们预防了中风后心功能不全。这种免疫靶向疗法有可能预防各种IL-1β介导的合并症，为二级预防免疫疗法提供框架。
英文摘要：
The medical burden of stroke extends beyond the brain injury itself and is largely determined by chronic comorbidities that develop secondarily. We hypothesized that these comorbidities might share a common immunological cause, yet chronic effects post-stroke on systemic immunity are underexplored. Here, we identify myeloid innate immune memory as a cause of remote organ dysfunction after stroke. Single-cell sequencing revealed persistent pro-inflammatory changes in monocytes/macrophages in multiple organs up to 3 months after brain injury, notably in the heart, leading to cardiac fibrosis and dysfunction in both mice and stroke patients. IL-1β was identified as a key driver of epigenetic changes in innate immune memory. These changes could be transplanted to naive mice, inducing cardiac dysfunction. By neutralizing post-stroke IL-1β or blocking pro-inflammatory monocyte trafficking with a CCR2/5 inhibitor, we prevented post-stroke cardiac dysfunction. Such immune-targeted therapies could potentially prevent various IL-1β-mediated comorbidities, offering a framework for secondary prevention immunotherapy.
论文信息：
论文题目：Innate immune memory after brain injury drives inflammatory cardiac dysfunction
期刊名称：Cell
时间期卷：在线2024-7-22685–700 (2024)
在线时间：2024年7月22日
研究亮点：
- 急性的脑缺血导致持续的先天免疫记忆
- 先天免疫记忆导致慢性中风后心功能不全
- IL-1β通过表观遗传修饰诱导中风后免疫
- 阻断 IL-1β 或单核细胞募集可预防心功能不全
材料方法：
