先天免疫训练恢复了促修复的髓系细胞功能，促进年老中枢神经系统的髓鞘再生，这一成果由德国慕尼黑大学Mikael Simons研究小组经过不懈努力而取得。相关论文于2024年7月24日发表在《免疫》杂志上。

在脱髓鞘模型中，课题组发现大量在衰老髓细胞中未被有效激活的基因显示出与染色质可及性受限相关的表观遗传修饰。去除小胶质细胞中的两种I类组蛋白去乙酰化酶足以恢复老年小鼠损伤组织的髓鞘再生能力。

该课题组人员使用卡介苗(bacillus Calmette-Guerin, BCG)，甲型肝炎减毒活疫苗训练先天免疫系统，检测脑内骨髓细胞的表观遗传重编程和髓磷脂碎片清除和病变恢复的功能恢复。他们的研究结果揭示了与衰老相关的骨髓功能衰退，以及如何通过先天免疫重编程来预防这种衰退。

据了解，随着年龄的增长，中枢神经系统再生能力的降低限制了脱髓鞘损伤后的功能恢复。先前的研究表明，髓磷脂碎片可以压倒小胶质细胞的代谢能力，从而阻碍衰老过程中的组织再生，但其潜在机制尚不清楚。

附：英文原文

Title: Innate immune training restores pro-reparative myeloid functions to promote remyelination in the aged central nervous system

Author: Vini Tiwari, Bharat Prajapati, Yaw Asare, Alkmini Damkou, Hao Ji, Lu Liu, Nawraa Naser, Garyfallia Gouna, Katarzyna B. Leszczyńska, Jakub Mieczkowski, Martin Dichgans, Qing Wang, Riki Kawaguchi, Zechuan Shi, Vivek Swarup, Daniel H. Geschwind, Marco Prinz, Ozgun Gokce, Mikael Simons

Issue&Volume: 2024-07-24

Abstract: The reduced ability of the central nervous system to regenerate with increasing age limits functional recovery following demyelinating injury. Previous work has shown that myelin debris can overwhelm the metabolic capacity of microglia, thereby impeding tissue regeneration in aging, but the underlying mechanisms are unknown. In a model of demyelination, we found that a substantial number of genes that were not effectively activated in aged myeloid cells displayed epigenetic modifications associated with restricted chromatin accessibility. Ablation of two class I histone deacetylases in microglia was sufficient to restore the capacity of aged mice to remyelinate lesioned tissue. We used Bacillus Calmette-Guerin (BCG), a live-attenuated vaccine, to train the innate immune system and detected epigenetic reprogramming of brain-resident myeloid cells and functional restoration of myelin debris clearance and lesion recovery. Our results provide insight into aging-associated decline in myeloid function and how this decay can be prevented by innate immune reprogramming.

DOI: 10.1016/j.immuni.2024.07.001

Source: https://www.cell.com/immunity/fulltext/S1074-7613(24)00348-0