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-γin 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.

Blocking immune cell infiltration of the central nervous system to tame neuroinflammation in amyotrophic lateral sclerosis / Garofalo, Stefano; Cocozza, Germana; Bernardini, Giovanni; Savage, Julie; Raspa, Marcello; Aronica, Eleonora; Tremblay, Marie-Eve; Ransohoff, Richard M; Santoni, Angela; Limatola, Cristina. - In: BRAIN, BEHAVIOR, AND IMMUNITY. - ISSN 1090-2139. - 105:(2022), pp. 1-14. [10.1016/j.bbi.2022.06.004]

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

Garofalo, Stefano
Primo
Conceptualization
;
Cocozza, Germana;Bernardini, Giovanni
Investigation
;
Raspa, Marcello;Aronica, Eleonora;Santoni, Angela
Penultimo
;
Limatola, Cristina
Ultimo
2022

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-γin 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.
2022
amyotrophic lateral sclerosis; astrocytes; immune cells; inflammation; microglia
01 Pubblicazione su rivista::01a Articolo in rivista
Blocking immune cell infiltration of the central nervous system to tame neuroinflammation in amyotrophic lateral sclerosis / Garofalo, Stefano; Cocozza, Germana; Bernardini, Giovanni; Savage, Julie; Raspa, Marcello; Aronica, Eleonora; Tremblay, Marie-Eve; Ransohoff, Richard M; Santoni, Angela; Limatola, Cristina. - In: BRAIN, BEHAVIOR, AND IMMUNITY. - ISSN 1090-2139. - 105:(2022), pp. 1-14. [10.1016/j.bbi.2022.06.004]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1644765
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