P2X7 receptor antagonists modulate experimental autoimmune neuritis via regulation of NLRP3 inflammasome activation and Th17 and Th1 cell differentiation.
Brilliant blue G
CD4+ T cell
Guillain–Barré syndrome
P2X7R
Journal
Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974
Informations de publication
Date de publication:
25 Mar 2024
25 Mar 2024
Historique:
received:
06
10
2023
accepted:
27
02
2024
medline:
26
3
2024
pubmed:
26
3
2024
entrez:
26
3
2024
Statut:
epublish
Résumé
Guillain-Barré syndrome (GBS), a post-infectious, immune-mediated, acute demyelinating disease of the peripheral nerves and nerve roots, represents the most prevalent and severe acute paralyzing neuropathy. Purinergic P2X7 receptors (P2X7R) play a crucial role in central nervous system inflammation. However, little is known about their role in the immune-inflammatory response within the peripheral nervous system. Initially, we assessed the expression of purinergic P2X7R in the peripheral blood of patients with GBS using flow cytometry and qRT-PCR. Next, we explored the expression of P2 X7R in CD4 P2X7R expression was elevated not only in the peripheral blood of patients with GBS but also in rats with EAN. In rats with EAN, inhibiting P2X7R with BBG alleviated neurological symptoms, reduced demyelination, decreased inflammatory cell infiltration of the peripheral nerves, and improved nerve conduction. BBG also limited the production of pro-inflammatory molecules, down-regulated the expression of P2X7R and NLRP3, and suppressed the differentiation of Th1 and Th17 cells, thus protecting against EAN. These effects collectively contribute to modifying the inflammatory environment and enhancing outcomes in EAN rats. Suppression of P2X7R relieved EAN manifestation by regulating CD4
Sections du résumé
BACKGROUND
BACKGROUND
Guillain-Barré syndrome (GBS), a post-infectious, immune-mediated, acute demyelinating disease of the peripheral nerves and nerve roots, represents the most prevalent and severe acute paralyzing neuropathy. Purinergic P2X7 receptors (P2X7R) play a crucial role in central nervous system inflammation. However, little is known about their role in the immune-inflammatory response within the peripheral nervous system.
METHODS
METHODS
Initially, we assessed the expression of purinergic P2X7R in the peripheral blood of patients with GBS using flow cytometry and qRT-PCR. Next, we explored the expression of P2 X7R in CD4
RESULTS
RESULTS
P2X7R expression was elevated not only in the peripheral blood of patients with GBS but also in rats with EAN. In rats with EAN, inhibiting P2X7R with BBG alleviated neurological symptoms, reduced demyelination, decreased inflammatory cell infiltration of the peripheral nerves, and improved nerve conduction. BBG also limited the production of pro-inflammatory molecules, down-regulated the expression of P2X7R and NLRP3, and suppressed the differentiation of Th1 and Th17 cells, thus protecting against EAN. These effects collectively contribute to modifying the inflammatory environment and enhancing outcomes in EAN rats.
CONCLUSIONS
CONCLUSIONS
Suppression of P2X7R relieved EAN manifestation by regulating CD4
Identifiants
pubmed: 38528529
doi: 10.1186/s12974-024-03057-z
pii: 10.1186/s12974-024-03057-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
73Subventions
Organisme : National Natural Science Foundation of China
ID : 82301523
Organisme : National Natural Science Foundation of China
ID : 82171277
Organisme : National Natural Science Foundation of China
ID : 82001280
Informations de copyright
© 2024. The Author(s).
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