Cxcl10+ monocytes define a pathogenic subset in the central nervous system during autoimmune neuroinflammation.
Amir GiladiLisa Katharina WagnerHanjie LiDorothea DörrChiara MedagliaFranziska PaulAnat ShemerSteffen JungSimon YonaMatthias MackAchim LeutzBjørt K KragesteenAlexander MildnerPublished in: Nature immunology (2020)
Multiple sclerosis (MS) is characterized by pathological inflammation that results from the recruitment of lymphoid and myeloid immune cells from the blood into the brain. Due to subset heterogeneity, defining the functional roles of the various cell subsets in acute and chronic stages of MS has been challenging. Here, we used index and transcriptional single-cell sorting to characterize the mononuclear phagocytes that infiltrate the central nervous system from the periphery in mice with experimentally induced autoimmune encephalomyelitis, a model of MS. We identified eight monocyte and three dendritic cell subsets at acute and chronic disease stages in which the defined transcriptional programs pointed toward distinct functions. Monocyte-specific cell ablation identified Cxcl10+ and Saa3+ monocytic subsets with a pathogenic potential. Transfer experiments with different monocyte and precursor subsets indicated that these Cxcl10+ and Saa3+ pathogenic cells were not derived from Ly6C+ monocytes but from early myeloid cell progenitors. These results suggest that blocking specific pathogenic monocytic subsets, including Cxcl10+ and Saa3+ monocytes, could be used for targeted therapeutic interventions.
Keyphrases
- peripheral blood
- dendritic cells
- single cell
- multiple sclerosis
- rna seq
- mass spectrometry
- drug induced
- immune response
- cell therapy
- liver failure
- ms ms
- gene expression
- regulatory t cells
- high throughput
- white matter
- bone marrow
- transcription factor
- induced apoptosis
- acute myeloid leukemia
- respiratory failure
- brain injury
- risk assessment
- stem cells
- climate change
- pi k akt
- blood brain barrier
- insulin resistance
- cell cycle arrest
- stress induced
- acute respiratory distress syndrome
- lipopolysaccharide induced