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

Date

2022

Authors

Garofalo, Stefano
Cocozza, Germana
Bernardini, Giovanni
Savage, Julie
Raspa, Marcello
Aronica, Eleonora
Tremblay, Marie-Eve
Ransohoff, Richard M.
Santoni, Angela
Limatola, Cristina

Journal Title

Journal ISSN

Volume Title

Publisher

Abstract

Neuroinflammation 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.

Description

Keywords

Amyotrophic lateral sclerosis, Immune cells, Inflammation, Astrocytes, Microglia

Citation

Garofalo, 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.2022.06.004