Microbiome-dependent intestinal MRC1+ VCAM1+ PD-L1+ dendritic cells migrate to the CNS and limit T-cell autoimmunity

However, the ability of intestinal dendritic cells (DCs) to migrate to the CNS and their contribution to neuroinflammation has not been previously established. Here, we combine photoconvertible transgenic Kaede mice, single-cell RNA sequencing, targeted genetic models, and human clinical samples to identify a distinct population of intestinal MRC1+ VCAM1+ PD-L1+ DCs (MVP+ DCs) that migrates to the CNS.

Type I interferon signaling driven by the commensal microbiota controls CNS-infiltrating gut-derived MVP+ DCs, which suppress CNS T-cell autoimmunity in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS) in a PD-L1 dependent manner. MVP+ DCs displaying immunosuppressive activity are detected in human blood; we also detected DCs displaying a transcriptional signature linked to gut-derived MVP+ DCs in blood and cerebrospinal fluid of MS patients.