神经炎症
肌萎缩侧索硬化
免疫系统
小胶质细胞
神经退行性变
中枢神经系统
炎症
神经科学
脊髓
医学
免疫学
生物
作者
Stefano Garofalo,Germana Cocozza,Giovanni Bernardini,Julie Savage,Marcello Raspa,Eleonora Aronica,Marie-Eve Tremblay,Richard M. Ransohoff,Angela Santoni,Cristina Limatola
标识
DOI:10.1016/j.bbi.2022.06.004
摘要
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 hSOD1 G93A and TDP43 A315T 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.
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