Epileptogenic triggers are multifactorial and not well understood. Here we aimed to address the hypothesis that inappropriate pro-inflammatory mechanisms contribute to the pathogenesis of refractory epilepsy (non-responsiveness to antiepileptic drugs) in human patients. We used single-cell cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to reveal the immunotranscriptome of surgically resected epileptic lesion tissues. Our approach uncovered a pro-inflammatory microenvironment, including extensive activation of microglia and infiltration of other pro-inflammatory immune cells. These findings were supported by ligand–receptor (LR) interactome analysis, which demonstrated potential mechanisms of infiltration and evidence of direct physical interactions between microglia and T cells. Together, these data provide insight into the immune microenvironment in epileptic tissue, which may aid the development of new therapeutics.

癫痫诱发因素是多因素的，目前尚不清楚。在这里，我们的目的是解决以下假设：不适当的促炎机制导致人类患者难治性癫痫（对抗癫痫药物无反应）的发病机制。我们通过测序（CITE-seq）对转录组和表位进行单细胞细胞索引，以揭示手术切除的癫痫病灶组织的免疫转录组。我们的方法揭示了促炎微环境，包括小胶质细胞的广泛激活和其他促炎免疫细胞的浸润。这些发现得到了配体-受体 (LR) 相互作用组分析的支持，该分析证明了潜在的浸润机制以及小胶质细胞和 T 细胞之间直接物理相互作用的证据。一起，