InnateImmuneCells 

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.

Ongoing Projects:

  • Interrogation of the growth factors, cytokines, chemokines and adhesion molecules that drive the differentiation of pro-regenerative neutrophils in vivo and orchestrate their migration to sites of CNS injury
  • Further characterization of the mechanism of action of pro-regenerative neutrophils and translation of the knowledge gained towards the development of novel reparative therapies for chronic CNS diseases
  • Generation of pro-regenerative neutrophils from bone marrow precursors in vitro (via culture with cytokine cocktails) for re-infusion to individuals with CNS injury as an autologous cellular therapy
  • Assessment of the therapeutic potential of pro-regenerative neutrophils in spinal cord and brain trauma models
  • Investigation of human pro-regenerative neutrophils

Related Publication:

  • Baldwin KT, Carbajal KS, Giger RJ, Segal BM. Neuroinflammation triggered by a β-glucan/ dectin-1 signaling enables CNS regeneration. Proc Nat Acad Sci 2015;112(8): 2581-6. PMID: 25675510

Related Funding:

  • National Institutes of Health (R01EY029159)
    A novel inflammatory cell with neuroprotective and neuroregenerative properties
  • National Institutes of Health (R01EY028350)
    Immune mediated regeneration of retinal ganglion cell axons following optic nerve trauma

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