https://onlinelibrary.wiley.com/doi/ful ... glia.23090
Notably, we found that C3d+ microglial clusters are associated with local production of C3 by neurons [...]. C3 biosynthesis might be triggered by injured axons via a retrograde signal or by the exposure of neurons to factors released in the microenvironment surrounding a lesion such as iron.
The significance of C3d+ microglial clusters formation is an important question. Their presence in the chronic but not acute disease stage [...] suggest that they are not part of an acute immune attack against myelinated axons, but may represent a physiological process linked to the progressive disease stage such as the elimination of myelin debris or transected axons.
Altogether, our data support the noninflammatory nature of C3d+ microglial clusters, pointing to the possibility that they are involved in the physiological removal of irreversibly damaged axons.
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