Microglial expression of CD83 governs cellular activation and restrains autoimmune neuroinflammation

Microglial activation during neuroinflammation is crucial for coordinating the immune response against neuronal tissue and the initial response of microglia determines the severity of neuroinflammatory diseases. CD83 has been associated with early activation of microglia in various disease settings albeit its functional relevance for microglial biology was still elusive. Thus, we conducted a thorough assessment of CD83 regulation in microglia as well as its impact on microglial mediated neuroinflammation. Here, we describe for the first time that CD83 expression in microglia is not only associated with cellular activation but also with pro-resolving functions. Conditional deletion of CD83 causes malfunctioning responses to myelin debris, which results in an over-activated state during autoimmune neuroinflammation. Subsequently, CD83-deficient microglia recruit more pathogenic immune cells to the central nervous system and deteriorate resolving mechanism, which exacerbates the disease. Thus, CD83 in microglia orchestrates cellular activation and consequently, also resolution of neuroinflammation. Conditional CD83 x CX3CR1-CreERT2 knock out mice and CX3CR1-CreERT2 control mice were subjected to experimental auto-immune encephalitis (EAE). Microglia was isolated by Fluorescence-activated cell sorting (FACS) according to the presence of CD45 (intermediate), CD11b, CX3CR1 and P2RY12 signal and analyzed using scRNAseq.