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Induction and Diverse Assessment Indicators of Experimental Autoimmune Encephalomyelitis
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Microglia suppress the secondary progression of autoimmune encephalomyelitis

Shogo Tanabe1,2, Shohei Saitoh2, Hisao Miyajima2,3

  • 1Department of Molecular Neuroscience, World Premier International, Immunology Frontier Research Center, Osaka University, Suita-shi, Osaka, Japan.

Glia
|May 21, 2019
PubMed

Insights

Microglia normally protect against secondary progressive multiple sclerosis (SPMS) by limiting T cell proliferation. Depleting microglia in a mouse model worsened SPMS, increasing inflammation and neurodegeneration.

Area of Science:

  • Neuroimmunology
  • Central Nervous System (CNS) Autoimmune Diseases

Background:

  • Secondary progressive multiple sclerosis (SPMS) is a debilitating CNS autoimmune disease with poorly understood pathology.
  • Microglia, the resident immune cells of the CNS, are implicated in various neurological conditions.

Purpose of the Study:

  • To investigate the role of microglia in the secondary progressive phase of experimental autoimmune encephalomyelitis (EAE), a mouse model of SPMS.
  • To determine if microglia modulate disease progression and T cell responses in established EAE.

Main Methods:

  • EAE was induced in nonobese diabetic mice.
  • Microglia were depleted during the secondary progressive phase using PLX3397, a colony-stimulating factor-1 receptor antagonist.
  • Disease progression, mortality, and spinal cord pathology (inflammation, demyelination, axonal damage) were assessed.
  • CD4+ T cell proliferation was quantified.

Main Results:

  • PLX3397 treatment significantly worsened EAE secondary progression and increased mortality.
  • Microglia depletion led to increased inflammation, demyelination, and axonal degeneration in the spinal cord.
  • The number of CD4+ T cells in the spinal cord significantly increased due to PLX3397-mediated proliferation.

Conclusions:

  • Microglia play a protective role in the secondary progressive phase of EAE.
  • Microglia suppress EAE progression by inhibiting the proliferation of CD4+ T cells within the CNS.
  • Targeting microglia depletion may exacerbate SPMS-like pathology.
Keywords:
PLX3397T cellmicroglianeuro-immune interactionssecondary progressive multiple sclerosis

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