Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation

TLDR

Myeloid cells in the CNS, including dendritic cells and macrophages, drive initiation and exacerbation of multiple sclerosis. The study used high‑throughput single‑cell RNA‑seq and intravital microscopy to map myeloid subsets in the EAE mouse model of MS. During EAE, microglia and CNS‑associated macrophages expanded and diversified, while dendritic cells and monocyte‑derived cells—but not resident macrophages—presented antigen to pathogenic T cells, offering insights for MS therapy. Published in Science, issue p.

Abstract

A myeloid cell atlas of neuroinflammation Myeloid cells, such as dendritic cells and macrophages, in the central nervous system (CNS) play critical roles in the initiation and exacerbation of multiple sclerosis (MS). Jordão et al. combined high-throughput single-cell RNA sequencing and intravital microscopy to compile a transcriptional atlas of myeloid subsets in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Microglia and other CNS-associated macrophages expanded and transformed into various context-dependent subtypes during EAE. Furthermore, dendritic cells and monocyte-derived cells, but not resident macrophages, played a critical role by presenting antigen to pathogenic T cells. This exhaustive characterization may inform future therapeutic targeting strategies in MS. Science , this issue p. eaat7554