gms | German Medical Science

CD47 is overexpressed in actively remyelinating and in fully remyelinated MS lesions, so-called shadow plaques, whereas active MS lesions without signs of remyelination show a downregulation of this surface molecule. In this study we add a new role for CD47 which was previously described as an immunomodulatory surface molecule modulating macrophage activity in MS lesions. Here we propose that prolonged reduced signaling through CD47 leads to a remyelination failure of the lesions. CD47 is ubiquitously expressed on most cells of the human body including glia cells such as astrocytes and oligodendrocytes.

We demonstrate that direct CD47 stimulation in mixed glial neuronal cultures leads to an inhibition of oligodendrocyte precursor cell (OPC) differentiation, which keeps these cells in a differentiation state in which proliferation is possible. We further demonstrate that CD47 knockout animals show a lower remyelinating capacity in the cuprizone mouse model, an animal model in which feeding of the copper chelator cuprizone leads to a temporal demyelination within the corpus callosum and other brain regions, which is fully reversible after discontinuation of the cuprizone diet. Moreover, CD47 is highly upregulated in normal BL/6 mice during remyelination in this model. Our results indicate that CD47 signaling in early remyelinating lesions enables a sufficient regeneration of the oligodendrocyte progenitor pool; this is one precondition for proper remyelination of MS lesions.