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Proinflammatory IL-17 pathways dominate the architecture of the immunome in pediatric refractory epilepsy

Drug refractory epilepsy (RE) is a chronic neurological disease with varied etiology that represents a group of patients whose seizures do not respond to antiepileptic drugs. The immune system may have a role in seizure and epilepsy development, but the specific mechanisms of inflammation that lead...

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Autores principales: Kumar, Pavanish, Shih, Derrick Chan Wei, Lim, Amanda, Paleja, Bhairav, Ling, Simon, Li Yun, Lai, Li Poh, Su, Ngoh, Adeline, Arkachaisri, Thaschawee, Yeo, Joo Guan, Albani, Salvatore
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538358/
https://www.ncbi.nlm.nih.gov/pubmed/30912766
http://dx.doi.org/10.1172/jci.insight.126337
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author Kumar, Pavanish
Shih, Derrick Chan Wei
Lim, Amanda
Paleja, Bhairav
Ling, Simon
Li Yun, Lai
Li Poh, Su
Ngoh, Adeline
Arkachaisri, Thaschawee
Yeo, Joo Guan
Albani, Salvatore
author_facet Kumar, Pavanish
Shih, Derrick Chan Wei
Lim, Amanda
Paleja, Bhairav
Ling, Simon
Li Yun, Lai
Li Poh, Su
Ngoh, Adeline
Arkachaisri, Thaschawee
Yeo, Joo Guan
Albani, Salvatore
author_sort Kumar, Pavanish
collection PubMed
description Drug refractory epilepsy (RE) is a chronic neurological disease with varied etiology that represents a group of patients whose seizures do not respond to antiepileptic drugs. The immune system may have a role in seizure and epilepsy development, but the specific mechanisms of inflammation that lead to epileptogenesis and contribute to RE are unknown. Here, we used mass cytometry to comprehensively study the immune system of pediatric patients with RE and compared their immune profile and function with patients with age-matched autoimmune encephalitis (AIE) and healthy controls. Patients with RE and AIE displayed similar immune profiles overall, with changes in CD4(+) and CD8(+) T cell subsets and an unbalance toward proinflammatory IL-17 production. In addition, patients with RE uniquely showed an altered balance in NK cell subsets. A systems-level intercellular network analysis identified rewiring of the immune system, leading to loss of inhibitory/regulatory intercellular connections and emergence of proinflammatory pathogenic functions in neuroinflammatory immune cell networks in patients with AIE and RE. These data underscore the contribution of systemic inflammation to the pathogenesis of seizures and epileptogenesis and have direct translational implications in advancing diagnostics and therapeutics design.
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spelling pubmed-65383582019-05-31 Proinflammatory IL-17 pathways dominate the architecture of the immunome in pediatric refractory epilepsy Kumar, Pavanish Shih, Derrick Chan Wei Lim, Amanda Paleja, Bhairav Ling, Simon Li Yun, Lai Li Poh, Su Ngoh, Adeline Arkachaisri, Thaschawee Yeo, Joo Guan Albani, Salvatore JCI Insight Research Article Drug refractory epilepsy (RE) is a chronic neurological disease with varied etiology that represents a group of patients whose seizures do not respond to antiepileptic drugs. The immune system may have a role in seizure and epilepsy development, but the specific mechanisms of inflammation that lead to epileptogenesis and contribute to RE are unknown. Here, we used mass cytometry to comprehensively study the immune system of pediatric patients with RE and compared their immune profile and function with patients with age-matched autoimmune encephalitis (AIE) and healthy controls. Patients with RE and AIE displayed similar immune profiles overall, with changes in CD4(+) and CD8(+) T cell subsets and an unbalance toward proinflammatory IL-17 production. In addition, patients with RE uniquely showed an altered balance in NK cell subsets. A systems-level intercellular network analysis identified rewiring of the immune system, leading to loss of inhibitory/regulatory intercellular connections and emergence of proinflammatory pathogenic functions in neuroinflammatory immune cell networks in patients with AIE and RE. These data underscore the contribution of systemic inflammation to the pathogenesis of seizures and epileptogenesis and have direct translational implications in advancing diagnostics and therapeutics design. American Society for Clinical Investigation 2019-04-18 /pmc/articles/PMC6538358/ /pubmed/30912766 http://dx.doi.org/10.1172/jci.insight.126337 Text en © 2019 Kumar et al. http://creativecommons.org/licenses/by/4.0/ This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Article
Kumar, Pavanish
Shih, Derrick Chan Wei
Lim, Amanda
Paleja, Bhairav
Ling, Simon
Li Yun, Lai
Li Poh, Su
Ngoh, Adeline
Arkachaisri, Thaschawee
Yeo, Joo Guan
Albani, Salvatore
Proinflammatory IL-17 pathways dominate the architecture of the immunome in pediatric refractory epilepsy
title Proinflammatory IL-17 pathways dominate the architecture of the immunome in pediatric refractory epilepsy
title_full Proinflammatory IL-17 pathways dominate the architecture of the immunome in pediatric refractory epilepsy
title_fullStr Proinflammatory IL-17 pathways dominate the architecture of the immunome in pediatric refractory epilepsy
title_full_unstemmed Proinflammatory IL-17 pathways dominate the architecture of the immunome in pediatric refractory epilepsy
title_short Proinflammatory IL-17 pathways dominate the architecture of the immunome in pediatric refractory epilepsy
title_sort proinflammatory il-17 pathways dominate the architecture of the immunome in pediatric refractory epilepsy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538358/
https://www.ncbi.nlm.nih.gov/pubmed/30912766
http://dx.doi.org/10.1172/jci.insight.126337
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