中風(fēng)的醫(yī)療負(fù)擔(dān)超出了腦損傷本身，很大程度上是由繼發(fā)性慢性合并癥決定的。我們假設(shè)這些合并癥可能有一個共同的免疫學(xué)原因，但中風(fēng)后對全身免疫的慢性影響尚未得到充分探索。在這里，我們將髓系先天免疫記憶確定為中風(fēng)后遠(yuǎn)端器官功能障礙的原因。單細(xì)胞測序顯示，在腦損傷后長達(dá) 3 個月的多個器官（尤其是心臟）中，單核細(xì)胞/巨噬細(xì)胞持續(xù)存在促炎變化，導(dǎo)致小鼠和中風(fēng)患者的心臟纖維化和功能障礙。IL-1β被確定為先天免疫記憶表觀遺傳變化的關(guān)鍵驅(qū)動因素。這些變化可以移植到幼稚小鼠身上，誘發(fā)心功能障礙。通過中和中風(fēng)后的IL-1β或用CCR2/5抑制劑阻斷促炎性單核細(xì)胞運(yùn)輸，我們預(yù)防了中風(fēng)后心功能不全。這種免疫靶向療法有可能預(yù)防各種IL-1β介導(dǎo)的合并癥，為二級預(yù)防免疫療法提供框架。

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.

論文信息：

論文題目：Innate immune memory after brain injury drives inflammatory cardiac dysfunction

期刊名稱：Cell

時間期卷：在線2024-7-22pages685–700 (2024)

在線時間：2024年7月22日

研究亮點(diǎn)：

- 急性的腦缺血導(dǎo)致持續(xù)的先天免疫記憶

- 先天免疫記憶導(dǎo)致慢性中風(fēng)后心功能不全

- IL-1β通過表觀遺傳修飾誘導(dǎo)中風(fēng)后免疫

- 阻斷 IL-1β 或單核細(xì)胞募集可預(yù)防心功能不全

Cell: 腦缺血MCAO腦中風(fēng)Stroke造模品牌Doccol助力頂級期刊