Interleukin-9 protects from microglia- and TNF-mediated synaptotoxicity in experimental multiple sclerosis.
J Neuroinflammation
; 21(1): 128, 2024 May 14.
Article
em En
| MEDLINE
| ID: mdl-38745307
ABSTRACT
BACKGROUND:
Multiple sclerosis (MS) is a progressive neurodegenerative disease of the central nervous system characterized by inflammation-driven synaptic abnormalities. Interleukin-9 (IL-9) is emerging as a pleiotropic cytokine involved in MS pathophysiology.METHODS:
Through biochemical, immunohistochemical, and electrophysiological experiments, we investigated the effects of both peripheral and central administration of IL-9 on C57/BL6 female mice with experimental autoimmune encephalomyelitis (EAE), a model of MS.RESULTS:
We demonstrated that both systemic and local administration of IL-9 significantly improved clinical disability, reduced neuroinflammation, and mitigated synaptic damage in EAE. The results unveil an unrecognized central effect of IL-9 against microglia- and TNF-mediated neuronal excitotoxicity. Two main mechanisms emerged first, IL-9 modulated microglial inflammatory activity by enhancing the expression of the triggering receptor expressed on myeloid cells-2 (TREM2) and reducing TNF release. Second, IL-9 suppressed neuronal TNF signaling, thereby blocking its synaptotoxic effects.CONCLUSIONS:
The data presented in this work highlight IL-9 as a critical neuroprotective molecule capable of interfering with inflammatory synaptopathy in EAE. These findings open new avenues for treatments targeting the neurodegenerative damage associated with MS, as well as other inflammatory and neurodegenerative disorders of the central nervous system.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sinapses
/
Fator de Necrose Tumoral alfa
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Interleucina-9
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Microglia
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Encefalomielite Autoimune Experimental
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Camundongos Endogâmicos C57BL
Limite:
Animals
Idioma:
En
Revista:
J Neuroinflammation
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Itália