Neurons undergo IFN?-driven persistent epigenetic shifts and synaptic remodeling in the inflamed brain [ATAC-Seq]

Our study provides novel evidence that neuronal intrinsic epigenetic changes are established as a consequence of cytotoxic T cell-mediated immune attacks and persist long after the resolution of the inflammatory process and associate to long lasting synaptic loss Overall design: Chromatin accessibility of neurons derived from two neuroanatomical structures, namely hippocampus and brainstem, from control conditions and sequential disease timepoints of CD8 T cell-mediated encephalitis disease in a genetic background of NuTRAP transgenic and NuTRAP transgenic and IFNGR floxed mice

本研究提供了创新性证据，证实神经元内在表观遗传改变由细胞毒性T细胞介导的免疫攻击诱发，并在炎症反应消退后仍长期存在，且与持久的突触丢失密切相关。实验设计概况：针对NuTRAP转基因小鼠以及NuTRAP转基因IFNGR条件性敲除（floxed）小鼠的遗传背景，对其CD8 T细胞介导的脑炎模型设置对照组并采集疾病进展各时间点的神经元样本进行染色质可及性分析，所用神经元来源于两种神经解剖结构——海马体与脑干。