Myeloid cell plasticity in the evolution of central nervous system autoimmunity

Abstract

These observations demonstrate the heterogeneity of CNS myeloid cells, their evolution during the course of autoimmune demyelinating disease, and their plasticity on the single cell level. Future therapeutic strategies for disease modification in individuals with MS may be focused on accelerating the transition of CNS myeloid cells from a proinflammatory to a noninflammatory phenotype. Ann Neurol 2018;83:131-141.

CD11c+CD88+CD317+myeloid cells are critical mediators of persistent CNS autoimmunity

“…Pro-inflammatory myeloid cells during the pathogenesis of EAE have been described previously. Along these lines, central roles were reported for CCR2 + myeloid cells 44 , tissue resident classical DC 45 , microglia vs peripherally seeded monocytederived DC 20 , and pro inflammatory iNOS + macrophages vs anti-inflammatory Arg-1 + macrophages 45 . Our observations add to the complexity of categorizing myeloid cell populations into DC or monocytes/macrophages based on surface markers alone.…”

CNS-localized myeloid cells capture living invading T cells during neuroinflammation

“…Myeloid cell activation in the CNS is a hallmark of inflammatory lesions in EAE and MS, where myeloid cells of the brain continuously scan their environment, mediating both detrimental and tissue homeostatic functions, presumably depending on the context (Giles et al, 2018; Heneka et al, 2014; Jolivel et al, 2015; Nimmerjahn et al, 2005). Although it is well known that pathogenic Th17 cells invade the CNS during MS and EAE, thereby mediating inflammation and neuronal degeneration (Dendrou et al, 2015; Goverman, 2009), whether they engage resident myeloid cells directly has not been clarified.…”

“…Variable roles of resident myeloid cells of the brain have been reported in both the healthy and diseased state (Giles et al, 2018; Schafer and Stevens, 2015; Shemer et al, 2015). Aside from defending against invading pathogens, they also use their phagocytic capacity to clear cellular debris, infectious agents, or neurons undergoing programmed cell death, thereby attempting to maintain tissue homeostasis.…”

“…Inhibition of myeloid cell function repressed clinical EAE severity in a bone marrow chimera model and reduced both axonal destruction (Heppner et al, 2005) and secretion of proinflammatory cytokines and chemokines in the spinal cord (Goldmann et al, 2013). However, myeloid cell function was also reported to change properties context dependently in the course of the disease (Giles et al, 2018). In contrast to their well-characterized neurotoxic ability, a potential neuroprotective function of CNS myeloid cells is far less understood (Kerschensteiner et al, 2003).…”

Heterogeneous macrophages: Supersensors of exogenous inducing factors

“…Thus, promoting the polarization of macrophages to alternative activation states may be a strategy for the treatment of type 2 diabetes . Giles et al found that in multiple sclerosis (MS) and engineered autoimmune encephalomyelitis (EAE) animal models, molecular phenotypic changes occur in the main infiltrating myeloid cells and microglia in the central nervous system (CNS), including differences in the expression levels of pro‐inflammatory markers (iNOS) and noninflammatory markers (CD206 and Arg1), during the progression from the EAE activity period to the remission period. Based on these observations, the research team believes that accelerating the transformation of CNS myeloid cells from a pro‐inflammatory phenotype to a noninflammatory phenotype could be a central strategy for improving the disease status of MS patients in future.…”