Bibliographic Details
| Title: |
Interleukin-9 protects from microglia- and TNF-mediated synaptotoxicity in experimental multiple sclerosis. |
| Authors: |
Guadalupi, Livia, Vanni, Valentina, Balletta, Sara, Caioli, Silvia, De Vito, Francesca, Fresegna, Diego, Sanna, Krizia, Nencini, Monica, Donninelli, Gloria, Volpe, Elisabetta, Mariani, Fabrizio, Battistini, Luca, Stampanoni Bassi, Mario, Gilio, Luana, Bruno, Antonio, Dolcetti, Ettore, Buttari, Fabio, Mandolesi, Georgia, Centonze, Diego, Musella, Alessandra |
| Source: |
Journal of Neuroinflammation; 5/14/2024, Vol. 21, p1-16, 16p |
| Subject Terms: |
MULTIPLE sclerosis, INTERLEUKIN-9, CENTRAL nervous system diseases, DISEASE progression, CENTRAL nervous system |
| 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. [ABSTRACT FROM AUTHOR] |
|
Copyright of Journal of Neuroinflammation is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Complementary Index |
|
Full text is not displayed to guests. |
Login for full access.
|
