Myelin debris derived from destroyed axons can act as a stimulatory agent in the inflamed CNS. Even in the steady state, we have observed that CD83-deficient microglia express less Trem2 and Lpl, which are important for uptake and disposal of myelin debris (see Fig. 3d), and this disparity got even more pronounced in EAE-derived microglia (Fig. 5h). Recent studies have shown that Lpl-deficient microglia exhibit an inflammatory profile due to accumulation of intracellular lipid droplets42. Thus, we assessed the gene expression of myelin-treated microglia and discovered that CD83-deficient microglia responded with increased expression of Ccl2 (Fig. 5i). Since Trem2 and Lpl form a functional unit for disposal of accumulating myelin debris in the CNS43, we examined the ability of CD83-deficient microglia to phagocytose myelin debris and found that microglia from CD83ΔMG mice were equally capable of ingesting fluorescently labeled myelin (Supplementary Fig. 4f). Collectively, these data provide evidence that neuro-inflammatory events are potentiated by CD83-deficiency through over-activation of microglial cells, most likely due to exaggerated responses to danger signals, such as myelin debris.
