Blocking immune cell infiltration of the central nervous system to tame neuroinflammation in amyotrophic lateral sclerosis

dc.contributor.authorGarofalo, Stefano
dc.contributor.authorCocozza, Germana
dc.contributor.authorBernardini, Giovanni
dc.contributor.authorSavage, Julie
dc.contributor.authorRaspa, Marcello
dc.contributor.authorAronica, Eleonora
dc.contributor.authorTremblay, Marie-Eve
dc.contributor.authorRansohoff, Richard M.
dc.contributor.authorSantoni, Angela
dc.contributor.authorLimatola, Cristina
dc.date.accessioned2024-02-02T20:13:41Z
dc.date.available2024-02-02T20:13:41Z
dc.date.copyright2022en_US
dc.date.issued2022
dc.description.abstractNeuroinflammation is one of the main hallmarks of amyotrophic lateral sclerosis (ALS). Recently, peripheral immune cells were discovered as pivotal players that promptly participate in this process, speeding up neurodegeneration during progression of the disease. In particular, infiltrating T cells and natural killer cells release inflammatory cytokines that switch glial cells toward a pro-inflammatory/detrimental phenotype, and directly attack motor neurons with specific ligand-receptor signals. Here, we assessed the presence of lymphocytes in the spinal cord of sporadic ALS patients. Furthermore, we demonstrate that blocking the extravasation of immune cells in the central nervous system using Natalizumab (NAT), an antibody for the α4 integrin, reduces the level of interferon-γ in the spinal cord of ALS mouse models, such as the hSOD1G93A and TDP43A315T mice, modifying microglia and astrocytes phenotype, increasing motor neuron number and prolonging the survival time. Taken together, our results establish a central role for the immune cells as drivers of inflammation in ALS.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipThis work was supported by AIRC 22,329 2018, ARISLA NKINALS 2019 to S.G.; PRIN 2017 20178L7WRS_001, AIRC 2019: IG-23010 to C. L. M.E.T. is a Tier II Canada Research Chair in Neurobiology of Aging and Cognition. ALS Stichting grant “The Dutch ALS Tissue Bank” (A.E.).en_US
dc.identifier.citationGarofalo, S., Cocozza, G., Bernardini, G., Savage, J., Raspa, M., Aronica, E., ... Limatola, C. (2022). Blocking immune cell infiltration of the central nervous system to tame neuroinflammation in amyotrophic lateral sclerosis. Brain, Behavior, and Immunity, 105, 1-14. https://doi.org/10.1016/j.bbi.2022.06.004en_US
dc.identifier.urihttps://doi.org/10.1016/j.bbi.2022.06.004
dc.identifier.urihttp://hdl.handle.net/1828/15922
dc.language.isoenen_US
dc.subjectAmyotrophic lateral sclerosisen_US
dc.subjectImmune cellsen_US
dc.subjectInflammationen_US
dc.subjectAstrocytesen_US
dc.subjectMicrogliaen_US
dc.titleBlocking immune cell infiltration of the central nervous system to tame neuroinflammation in amyotrophic lateral sclerosisen_US
dc.typeArticleen_US

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