Amyotrophic lateral sclerosis (ALS) is a devastating fatal motor neuron disease, 
for which there is currently no cure or effective treatment. In this disease, 
local neuroinflammation develops along the disease course and contributes to its 
rapid progression. In several models of CNS pathologies, circulating immune 
cells were shown to display an indispensable role in the resolution of the 
neuroinflammatory response. The recruitment of such cells to the CNS involves 
activation of the choroid plexus (CP) of the brain for leukocyte trafficking, 
through a mechanism that requires IFN-γ signaling. Here, we found that in the 
mutant SOD1(G93A) (mSOD1) mouse model of ALS, the CP does not support leukocyte 
trafficking during disease progression, due to a local reduction in IFN-γ 
levels. Therapeutic immunization of mSOD1 mice with a myelin-derived peptide led 
to CP activation, and was followed by the accumulation of immunoregulatory 
cells, including IL-10-producing monocyte-derived macrophages and Foxp3(+) 
regulatory T cells, and elevation of the neurotrophic factors IGF-1 and GDNF in 
the diseased spinal cord parenchyma. The immunization resulted in the 
attenuation of disease progression and an increased life expectancy of the mSOD1 
mice. Collectively, our results demonstrate that recruitment of immunoregulatory 
cells to the diseased spinal cord in ALS, needed for fighting off the pathology, 
can be enhanced by transiently boosting peripheral immunity to myelin antigens.