In the first study, Lock et al. compared transcripts from the two lesion types and showed differential gene expression between them, uncovering several genes not previously thought to be important in MS. Comparing tissues from individuals with and without MS revealed genes whose expression was increased in MS samples, among them were the immune response molecules, major histocompatibility complex class II and immunoglobulin G; complement molecules; B-cell and macrophage-specific molecules; adhesion molecules, integrin β4 and P-selectin; and several pro-inflammatory cytokines. Expression of neuron-associated genes and those encoding proteins associated with myelin production was decreased, suggesting that the capacity for tissue repair is compromised in MS patients.
Some of these differentially regulated gene products were chosen by the authors to test in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, as potential therapeutic targets. The first study revealed that the immunoglobulin Fcγ receptor was upregulated in chronic lesions. Satisfyingly, the authors saw that Fcγ-receptor-knockout mice, in which EAE was induced, had less severe acute disease and no chronic disease, compared to wild-type mice with EAE. The first study also showed that granulocyte-colony-stimulating factor (G-CSF) was upregulated in acute lesions. The authors showed that early treatment of EAE mice with G-CSF decreased the severity of the disease but that later treatment had no effect, suggesting that G-CSF might be a regulatory molecule that naturally suppresses acute attacks.
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