Single-cell transcriptomics and surface epitope detection in human brain epileptic lesions identifies pro-inflammatory signaling

Nat Neurosci. 2022 Jul;25(7):956-966. doi: 10.1038/s41593-022-01095-5. Epub 2022 Jun 23.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / pathology
  • Epilepsy* / genetics
  • Epitopes
  • Humans
  • Microglia / pathology
  • Transcriptome*

Substances

  • Epitopes