In published studies we have examined the role of myeloid cells during multiple sclerosis (MS) and the animal model, experimental autoimmune encephalomyelitis (EAE). We have found that CNS-infiltrating myeloid cells are heterogeneous, and include monocytes, macrophages, classical dendritic cells, and myeloid dendritic cells. Macrophages and myeloid dendritic cells transition from a pro-inflammatory iNOS+ phenotype during disease exacerbation, to an immune-quiescent Arginase-1+ phenotype during remission. We are currently investigating the role of myeloid cell subsets in phagocytosing myelin, releasing toxic factors and activating pathogenic autoreactive T cells at peak disease, as well as in inducing regulatory T cells, promoting remyelination, and stimulating axon regeneration during recovery.
- Investigation of the factors that drive the evolution of CNS-infiltrating myeloid cells from a destructive to a neuroprotective phenotype during the course of EAE.
- Identification of the antigen presenting cells that activate autoreactive T cells within the CNS at disease onset
- Assessment of the impact of different CNS-infiltrating myeloid cell subsets on the viability, differentiation of oligodendrocyte precursor cells
- Assessment of the impact of CNS-infiltrating myeloid cell subsets on the viability of dissociated neurons, and on neurite outgrowth
- Development of therapies that block the development, accumulation, and function of pathogenic myeloid cells in the CNS, and/ or promote the development, accumulation, and function of neuroprotective myeloid cells.
- Analysis of myeloid subsets in postmortem MS lesions
- Giles, DA, Washnock-Schmid JM, Duncker PC, Dahlawi S, Ponath G, Pitt D, Segal BM. Myeloid cell plasticity in the evolution of central nervous system autoimmunity. Ann Neurol 2018;83(1): 131-141. PMID: 29283442
- Duncker PC, Stoolman JS, Huber AK, Segal BM. GM-CSF Promotes Chronic Disability in Experimental Autoimmune Encephalomyelitis by Altering the Composition of Central Nervous System-Infiltrating Cells, but is Dispensable for Disease Induction. J Immunol 2018; 200(3): 966-973. PMID: 29288202
- Segal BM and Giger RJ. Stable biomarker for plastic microglia. Proc Nat Acad Sci USA 2016;113(12): 3130-2. PMID: 26966229
- Rumble JM, Huber AK, Krishnamoorthy G, Srinivasan A, Giles DA, Zhang X, Wang L, Segal BM. Neutrophil-related factors as biomarkers in EAE and MS. J Exp Med 2015;212(1): 23-35. PMID: 25559893
- King IL, Dickendesher TL, Segal BM. Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease. Blood 2009;113(14): 3190-7. PMID: 19196868
- National Institutes of Health (R01NS105385)
Arginase-1 and iNOS expressing CNS myeloid cell subsets in EAE and MS
- National Institutes of Health (R21NS103215)
The mechanism of action of Granulocyte Macrophage-Colony Stimulating Factor in an animal model of Multiple Sclerosis