Single-cell transcriptomics and surface epitope detection in human brain epileptic lesions identifies pro-inflammatory signaling
Pavanish Kumar, Amanda Jin Mei Lim, Sharifah Nur Hazirah, Camillus Chua, Adeline Ngoh, Su Li Poh, Tong Hong Yeo, Jocelyn Lim, Simon Ling, Nursyuhadah Binte Sutamam, Enrico Petretto, David C.Y. Low, Li Zeng, Eng‐King Tan, Thaschawee Arkachaisri, Joo Guan Yeo, Florent Ginhoux, Derrick Chan, Salvatore Albani
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.