德国慕尼黑大学Arthur Liesz小组发现，脑损伤后的先天免疫记忆驱动炎症性心脏功能障碍。2024年7月22日，国际知名学术期刊《细胞》在线发表了这一成果。
研究人员表示，中风带来的医学负担不仅限于脑损伤本身，主要由随后发展的慢性共病决定。
研究人员假设这些共病可能共享一个共同的免疫学原因，但目前对中风后慢性系统性免疫效应的研究尚不足。研究人员发现中风后髓系先天性免疫记忆是远端器官功能障碍的原因。单细胞测序揭示了在脑损伤后长达三个月内，多器官中的单核细胞/巨噬细胞持续存在促炎性变化，特别是在心脏中，导致心脏纤维化和功能障碍，这一现象在小鼠和中风患者中均有观察到。IL-1β被确定为先天性免疫记忆中表观遗传变化的关键驱动因子。
这些变化可以通过移植到未经处理的小鼠体内，从而引起心脏功能障碍。通过中和中风后的IL-1β或使用CCR2/5抑制剂阻断促炎性单核细胞的迁移，研究人员成功预防了中风后的心脏功能障碍。这些免疫靶向疗法可能预防各种由IL-1β介导的共病，为次级预防免疫疗法提供了框架。
附：英文原文
Title: Innate immune memory after brain injury drives inflammatory cardiac dysfunction
Author: Alba Simats, Sijia Zhang, Denise Messerer, Faye Chong, Sude Bekarde, Aparna Sharma Chivukula, Jiayu Cao, Simon Besson-Girard, Felipe A. Montellano, Caroline Morbach, Olga Carofiglio, Alessio Ricci, Stefan Roth, Gemma Llovera, Rashween Singh, Yiming Chen, Severin Filser, Nikolaus Plesnila, Christian Braun, Hannah Spitzer, Ozgun Gokce, Martin Dichgans, Peter U. Heuschmann, Kinta Hatakeyama, Eduardo Beltrán, Sebastian Clauss, Boyan Bonev, Christian Schulz, Arthur Liesz
Issue&Volume: 2024-07-22
Abstract: 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.
DOI: 10.1016/j.cell.2024.06.028
Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00702-5