Probing the Role of Microglia in Relapsing-Remitting EAE

Microglia are the specialized phagocytes of the brain parenchyma. In multiple sclerosis (MS), an autoimmune disease targeted at the CNS, microglia phagocytose cell debris and upregulate immune-related transcripts. However, it is not clear whether microglia play a beneficial or detrimental role, whether they interact with the infiltrating immune cells and whether or not these cells mediate recovery. Here, we used the Relapsing-Remitting Experimental Autoimmune Encephalomyelitis (RR-EAE) mouse model for MS on SJL*B6 F1 hybrids to study the role of microglia in different stages of the disease, focusing on their contributions to recovery and relapse. Using the RiboTag approach in Cx3cr1^CreER:Rpl22^HA mice ¹, we revealed that microglia actively translate inhibitory molecules, such as Lag3, PDL1 and IL18bp. Moreover, microglia depletion experiments indicate a delayed recovery accompanied by T cell accumulation in the brains. Collectively, our results suggest that the presence and immune competence of microglia might be important for the recovery phase in RR-EAE. Inhibitory molecules expressed by microglia could mediate recovery, however the precise molecular mechanism by which this takes place remains under investigation.