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

Kumar, Pavanish, Lim, Amanda, Hazirah, Sharifah Nur, Chua, Camillus Jian Hui, Ngoh, Adeline, Poh, Su Li, Yeo, Tong Hong, Lim, Jocelyn, Ling, Simon, Sutamam, Nursyuhadah Binte, Petretto, Enrico, Low, David Chyi Yeu, Zeng, Li, Tan, Eng-King, Arkachaisri, Thaschawee, Yeo, Joo Guan, Ginhoux, Florent, Chan, Derrick, Albani, Salvatore·2022·Nature Neuroscience
DOI 10.1038/s41593-022-01095-5PMC PMC9276529
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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.

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Metadata

Authors
Kumar, P., Lim, A., Hazirah, S. N., Chua, C. J. H., Ngoh, A., Poh, S. L., Yeo, T. H., Lim, J., Ling, S., Sutamam, N. B., Petretto, E., Low, D. C. Y., Zeng, L., Tan, E.-K., Arkachaisri, T., Yeo, J. G., Ginhoux, F., Chan, D., & Albani, S.
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2022-06-23
Volume
25
Issue
7
Pages
956-966
ISSN
  • 1097-6256
  • 1546-1726
DOI
10.1038/s41593-022-01095-5
PMC
PMC9276529
Cited by
142
References
6
Language
en
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